CClinicalTrials.gg
CompletedNCT03263442Updated Oct 19, 2021Results posted

High Dose Intravenous Thiamine for the Prevention of Delirium in Allogeneic Hematopoietic Stem Cell Transplantation

A Phase 2 interventional study of Thiamine and Normal saline in Hematopoietic Stem Cell Transplantation, Delirium and Thiamine Deficiency, sponsored by UNC Lineberger Comprehensive Cancer Center. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2021-10-19.

Sponsored by UNC Lineberger Comprehensive Cancer Center · Phase 2, Interventional, and Prevention

Phase
Phase 2
Study type
Interventional
Enrollment
66
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

Purpose: To conduct a randomized controlled pilot study investigating the use of high dose intravenous (IV) thiamine to prevent delirium and mitigate the long-term effects of delirium, including health-related quality of life (HRQOL), functional status, and neuropsychiatric outcomes, in patients admitted to University of North Carolina (UNC) Hospital for allogeneic hematopoietic stem cell transplant (HSCT).

Participants: 60 adult inpatients admitted to the UNC Bone Marrow Transplant Unit for allogeneic stem cell transplant.

Procedures (methods): Participants will be admitted for allogeneic HSCT and on the day after transplant randomized to seven days of high dose IV thiamine or placebo. Thiamine levels will be measured weekly and participants will be assessed for evidence of delirium using validated measures. Validated measures will also be used to assess cognitive function, depression, post-traumatic stress symptoms, functional status, and HRQOL prior to hospitalization and at one, three, and six months after transplant.

Read the detailed description

Delirium is a common and potentially preventable neuropsychiatric complication in cancer patients receiving hematopoietic stem cell transplantation (HSCT) that has profound consequences. Among cancer patients hospitalized for HSCT, delirium occurs in approximately 40% of patients and increases the risk of mortality. Long-term, delirium in this population results in worse physical health, mental health, and quality of life. Though strategies to prevent delirium have the potential to significantly improve the lives of people living with cancer, research in this area is extremely limited. Thiamine deficiency is also ubiquitous during HSCT and a known contributor to the development of delirium in other patient populations. High dose intravenous (IV) thiamine is an evidence-based and promising treatment for delirium, but no one has studied IV thiamine as a prevention strategy.

This is a randomized double-blind controlled trial in participants undergoing allogeneic HSCT to determine if high dose IV thiamine can prevent delirium and minimize the deleterious impact of delirium on health-related quality of life (HRQOL), functional status, and other neuropsychiatric outcomes. The investigators will recruit 60 patients admitted for allogeneic HSCT at UNC, randomize them to treatment with high dose IV thiamine (n = 30) versus placebo (n = 30), and systematically evaluate all participants for delirium and related comorbidities. The investigators will use the Delirium Rating Scale (DRS) to measure the severity and duration of delirium immediately prior to transplant and after HSCT until 30 days post-transplant or discharge. If delirium is identified, the DRS will be administered daily until delirium resolves. The investigators will obtain thiamine levels and other laboratory parameters associated with delirium the day after transplant, and continue to monitor thiamine levels weekly thereafter. The investigators will also monitor HRQOL, functional status, depression, post-traumatic stress symptoms, and cognitive function prior to transplant and at one, three, and six months after transplant to elucidate the persistent impact of delirium in this population and the potential for thiamine to mitigate these negative outcomes.

02

Conditions studied

  • Hematopoietic Stem Cell Transplantation
  • Delirium
  • Thiamine Deficiency
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Admission to the UNC Hospital Bone Marrow Transplant Unit for allogeneic stem cell transplant
  • At least 18 years of age
  • Able to speak English
  • Able to provide informed consent

Exclusion criteria

Exclusion Criteria:

  • A history of adverse reaction to IV thiamine
  • Pregnancy, confirmed by a negative pregnancy test within 30 days of study enrollment
04

Study design

Phase
Phase 2
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
66 participants (actual)

Study arms

  • Experimental
    Intervention

    Thiamine 200 mg IV

    Drug: Thiamine

  • Placebo comparator
    Control

    Normal saline IV

    Drug: Normal saline

Interventions

  • DrugThiamine

    200 mg IV three times daily for seven days

    Also known as: Thiamine Hydrochloride Injection

  • DrugNormal saline

    Normal saline IV three times daily for seven days

    Also known as: Placebo

05

What researchers measure

Primary outcomes

  1. Percentage of Participants With Delirium

    Delirium incidence will be measured using the Delirium Rating Scale (DRS). The DRS is a is a 10-item, clinician-rated scale that rates the severity of delirium symptoms over a 24-hour period using all available information from the patient interview, mental status examination, medical history and tests, nursing observations, and family reports. The maximum possible score is 32. Higher scores suggest more severe symptoms. A cut-off score of \> 12 has been suggested to distinguish patients with delirium from patients with other neuropsychiatric disorders. Delirium incidence will be defined as at least one assessment with DRS \> 12.

    Time frame: Assessments will occur in the week prior to transplant, then 3 times weekly post-transplant until 30 days post-transplant or discharge, whichever comes first.

Secondary outcomes

  1. Delirium Severity

    Delirium severity will be measured using the Delirium Rating Scale (DRS). The DRS is a is a 10-item, clinician-rated scale that rates the severity of delirium symptoms over a 24-hour period using all available information from the patient interview, mental status examination, medical history and tests, nursing observations, and family reports. The score ranges from 0 to 32 with higher scores reflecting more severe symptoms. A cut-off score of \> 12 has been suggested to distinguish patients with delirium from patients with other neuropsychiatric disorders. The DRS medians and ranges are reported for each group at baseline and in each week of hospitalization for thiamine and placebo groups.

    Time frame: Assessments will occur in the week prior to transplant (baseline), then at least 3 times post-transplant on a weekly basis until 30 days post-transplant or discharge, whichever comes first, up to week 5

  2. Delirium Duration

    Delirium duration will be measured using the Delirium Rating Scale (DRS). The DRS is a is a 10-item, clinician-rated scale that rates the severity of delirium symptoms over a 24-hour period using all available information from the patient interview, mental status examination, medical history and tests, nursing observations, and family reports. The maximum possible score is 32. Higher scores suggest more severe symptoms. A cut-off score of \> 12 has been suggested to distinguish patients with delirium from patients with other neuropsychiatric disorders. Delirium duration will be reported as number of consecutive days during which DRS \> 12.

    Time frame: Assessments will occur in the week prior to transplant, then 3 times weekly post-transplant until 30 days post-transplant or discharge, whichever comes first.

  3. Concentration of Thiamine Status Stratified by Delirium Status

    The relationship between thiamine levels at the end of the seven day administration of thiamine and the development of delirium at any point during the thirty days post-transplant or the post-transplant hospitalization, whichever comes first, will be examined. Thiamine levels (nmol/L) are presented in participants who did and did not experience delirium.

    Time frame: From end of 7-day intervention period until the development of delirium at any point during the post-transplant hospitalization up to a maximum of 30 days

  4. Change in Health-related Quality of Life Scores (Month 1)

    HRQOL will be assessed using the Functional Assessment of Cancer Therapy - Bone Marrow Transplant (FACT-BMT). The FACT-BMT is a 47-item self-administered assessment which asks individuals to rate questions related to physical, social/family, emotional, and functional well-being on a 5-point Likert Scale (0, not at all to 4, very much). Scores are summed across the items, resulting in a score from 0 to 148, with higher scores indicating better quality of life. Negative change scores indicate worse HRQOL with time.

    Time frame: From baseline to one month post-transplant

  5. Change in Health-related Quality of Life Scores (Month 3)

    HRQOL will be assessed using the Functional Assessment of Cancer Therapy - Bone Marrow Transplant (FACT-BMT). The FACT-BMT is a 47-item self-administered assessment which asks individuals to rate questions related to physical, social/family, emotional, and functional well-being on a 5-point Likert Scale (0, not at all to 4, very much). Scores are summed across the items, resulting in a score from 0 to 148, with higher scores indicating better quality of life. Negative change scores indicate worse HRQOL with time.

    Time frame: Baseline to three months post-transplant

  6. Change in Health-related Quality of Life Scores (Month 6)

    HRQOL will be assessed using the Functional Assessment of Cancer Therapy - Bone Marrow Transplant (FACT-BMT). The FACT-BMT is a 47-item self-administered assessment which asks individuals to rate questions related to physical, social/family, emotional, and functional well-being on a 5-point Likert Scale (0, not at all to 4, very much). Scores are summed across the items, resulting in a score from 0 to 148, with higher scores indicating better quality of life. Negative change scores indicate worse HRQOL with time.

    Time frame: Baseline to six months post-transplant

  7. Change in Depression Scores (Month 1)

    Depression will be assessed using the Patient Reported Outcomes Measurement Information System - Depression (PROMIS-D) 8a short form. Scores for all PROMIS measures are reported on the T-score metric in which the mean=50 and standard deviation (SD) = 10 are centered on the general population means. Higher scores represent greater degrees of mood symptoms. Positive change scores indicate worse mood over time.

    Time frame: Baseline to one month post-transplant

  8. Change in Depression Scores (Month 3)

    Depression will be assessed using the Patient Reported Outcomes Measurement Information System - Depression (PROMIS-D) 8a short form. Scores for all PROMIS measures are reported on the T-score metric in which the mean=50 and standard deviation (SD) = 10 are centered on the general population means. Higher scores represent greater degrees of mood symptoms. Positive change scores indicate worse mood over time.

    Time frame: Baseline to three months post-transplant

  9. Change in Depression Scores (Month 6)

    Depression will be assessed using the Patient Reported Outcomes Measurement Information System - Depression (PROMIS-D) 8a short form. Scores for all PROMIS measures are reported on the T-score metric in which the mean=50 and standard deviation (SD) = 10 are centered on the general population means. Higher scores represent greater degrees of mood symptoms. Positive change scores indicate worse mood over time.

    Time frame: Baseline to six months post-transplant

  10. Change in Post-traumatic Stress Symptom Scores (Month 1)

    Post-traumatic stress symptoms will be measured using the Post Traumatic Stress Syndrome Scale 14 (PTSS-14). The PTSS-14 is a 14-item self-administered assessment. Questions are on a 7-point Likert-type Scale (1, never to 7, always) resulting in a total score between 14 and 98. Higher scores represent a more likely diagnosis of post-traumatic stress disorder (PTSD). Positive change scores indicate worse post-traumatic stress over time.

    Time frame: Baseline to one month post-transplant

  11. Change in Post-traumatic Stress Symptom Scores (Month 3)

    Post-traumatic stress symptoms will be measured using the Post Traumatic Stress Syndrome Scale 14 (PTSS-14). The PTSS-14 is a 14-item self-administered assessment. Questions are on a 7-point Likert-type Scale (1, never to 7, always) resulting in a total score between 14 and 98. Higher scores represent a more likely diagnosis of post-traumatic stress disorder (PTSD). Positive change scores indicate worse post-traumatic stress over time.

    Time frame: Baseline to three months post-transplant

  12. Change in Post-traumatic Stress Symptom Scores (Month 6)

    Post-traumatic stress symptoms will be measured using the Post Traumatic Stress Syndrome Scale 14 (PTSS-14). The PTSS-14 is a 14-item self-administered assessment. Questions are on a 7-point Likert-type Scale (1, never to 7, always) resulting in a total score between 14 and 98. Higher scores represent a more likely diagnosis of post-traumatic stress disorder (PTSD). Positive change scores indicate worse post-traumatic stress over time.

    Time frame: Baseline to six months post-transplant

  13. Change in Cognitive Function Scores (Month 1)

    Cognitive function will be assessed using the Montreal Cognitive Assessment (MOCA). The MOCA is a clinician-administered tool with scores ranging from 0 to 30. Lower scores indicate worse cognitive function. Scores ≤ 25 are considered clinically significant. Positive change scores indicate better function with time.

    Time frame: From baseline to one month post-transplant

  14. Change in Cognitive Function Scores (Month 3)

    Cognitive function will be assessed using the Montreal Cognitive Assessment (MOCA). The MOCA is a clinician-administered tool with scores ranging from 0 to 30. Lower scores indicate worse cognitive function. Scores ≤ 25 are considered clinically significant. Positive change scores indicate better function with time.

    Time frame: Baseline to three months post-transplant

  15. Change in Cognitive Function Scores (Month 6)

    Cognitive function will be assessed using the Montreal Cognitive Assessment (MOCA). The MOCA is a clinician-administered tool with scores ranging from 0 to 30. Lower scores indicate worse cognitive function. Scores ≤ 25 are considered clinically significant. Positive change scores indicate better function with time.

    Time frame: From baseline to six months post-transplant

  16. Change in Functional Status Scores (Month 1)

    Functional status will be measured using the Eastern Cooperative Oncology Group (ECOG) performance scale. ECOG performance status is a single question scored on a 6-point scale (range 0 to 5) with higher scores representing greater physical restriction due to illness. Negative change scores indicate better function with time.

    Time frame: Baseline to one month post-transplant

  17. Change in Functional Status Scores (Month 3)

    Functional status will be measured using the Eastern Cooperative Oncology Group (ECOG) performance scale. ECOG performance status is a single question scored on a 6-point scale (range 0 to 5) with higher scores representing greater physical restriction due to illness. Negative change scores indicate better function with time.

    Time frame: From baseline to three months post-transplant

  18. Change in Functional Status Scores (Month 6)

    Functional status will be measured using the Eastern Cooperative Oncology Group (ECOG) performance scale. ECOG performance status is a single question scored on a 6-point scale (range 0 to 5) with higher scores representing greater physical restriction due to illness. Negative change scores indicate better function with time.

    Time frame: Baseline to six months post-transplant

06

Results

Posted Apr 26, 2021

Participant flow

Participants were recruited from the UNC Bone Marrow Transplant and Cellular Therapies Unit from October 2017 through February 2020.

Inpatient Phase
Participant flow — Inpatient Phase
MilestoneInterventionControl
Started3034
Completed2833
Not completed21
Withdrew: Death10
Withdrew: Withdrawal by subject10
Withdrew: Inadequate drug exposure01
1-month Follow-Up
Participant flow — 1-month Follow-Up
MilestoneInterventionControl
Started2833
Completed2733
Not completed10
Withdrew: Lost to follow-up10
3-month Follow-Up
Participant flow — 3-month Follow-Up
MilestoneInterventionControl
Started2733
Completed2630
Not completed13
Withdrew: Lost to follow-up13
6-month Follow-Up
Participant flow — 6-month Follow-Up
MilestoneInterventionControl
Started2630
Completed2428
Not completed22
Withdrew: Lost to follow-up22

Outcome measures

PrimaryPercentage of Participants With Delirium

Delirium incidence will be measured using the Delirium Rating Scale (DRS). The DRS is a is a 10-item, clinician-rated scale that rates the severity of delirium symptoms over a 24-hour period using all available information from the patient interview, mental status examination, medical history and tests, nursing observations, and family reports. The maximum possible score is 32. Higher scores suggest more severe symptoms. A cut-off score of \> 12 has been suggested to distinguish patients with delirium from patients with other neuropsychiatric disorders. Delirium incidence will be defined as at least one assessment with DRS \> 12.

Time frame:
Assessments will occur in the week prior to transplant, then 3 times weekly post-transplant until 30 days post-transplant or discharge, whichever comes first.
Reported as:
Number · percentage of participants
Percentage of Participants With Delirium
percentage of participantsInterventionControl
Percentage of Participants With Delirium2521
SecondaryDelirium Severity

Delirium severity will be measured using the Delirium Rating Scale (DRS). The DRS is a is a 10-item, clinician-rated scale that rates the severity of delirium symptoms over a 24-hour period using all available information from the patient interview, mental status examination, medical history and tests, nursing observations, and family reports. The score ranges from 0 to 32 with higher scores reflecting more severe symptoms. A cut-off score of \> 12 has been suggested to distinguish patients with delirium from patients with other neuropsychiatric disorders. The DRS medians and ranges are reported for each group at baseline and in each week of hospitalization for thiamine and placebo groups.

Time frame:
Assessments will occur in the week prior to transplant (baseline), then at least 3 times post-transplant on a weekly basis until 30 days post-transplant or discharge, whichever comes first, up to week 5
Reported as:
Median · score on a scale
Delirium Severity
score on a scaleInterventionControl
Baseline4.0 (2.0 to 8.0)4.0 (2.0 to 7.0)
Week 14.83 (3.0 to 9.0)4.67 (2.67 to 15.00)
Week 26.50 (2.67 to 20.33)5.33 (2.33 to 16.00)
Week 36.33 (1.00 to 18.60)5.17 (2.00 to 17.80)
Week 45.50 (4.00 to 20.00)6.00 (5.00 to 13.50)
Week 520.00 (20.00 to 20.00)7.50 (4.00 to 8.00)
SecondaryDelirium Duration

Delirium duration will be measured using the Delirium Rating Scale (DRS). The DRS is a is a 10-item, clinician-rated scale that rates the severity of delirium symptoms over a 24-hour period using all available information from the patient interview, mental status examination, medical history and tests, nursing observations, and family reports. The maximum possible score is 32. Higher scores suggest more severe symptoms. A cut-off score of \> 12 has been suggested to distinguish patients with delirium from patients with other neuropsychiatric disorders. Delirium duration will be reported as number of consecutive days during which DRS \> 12.

Time frame:
Assessments will occur in the week prior to transplant, then 3 times weekly post-transplant until 30 days post-transplant or discharge, whichever comes first.
Reported as:
Mean · days
Delirium Duration
daysInterventionControl
Delirium Duration2.0 ± 1.24.4 ± 4.7
SecondaryConcentration of Thiamine Status Stratified by Delirium Status

The relationship between thiamine levels at the end of the seven day administration of thiamine and the development of delirium at any point during the thirty days post-transplant or the post-transplant hospitalization, whichever comes first, will be examined. Thiamine levels (nmol/L) are presented in participants who did and did not experience delirium.

Time frame:
From end of 7-day intervention period until the development of delirium at any point during the post-transplant hospitalization up to a maximum of 30 days
Reported as:
Mean · nmol/L
Concentration of Thiamine Status Stratified by Delirium Status
nmol/LDeliriumNo Delirium
Concentration of Thiamine Status Stratified by Delirium Status115.6 ± 69.393.8 ± 28.5
SecondaryChange in Health-related Quality of Life Scores (Month 1)

HRQOL will be assessed using the Functional Assessment of Cancer Therapy - Bone Marrow Transplant (FACT-BMT). The FACT-BMT is a 47-item self-administered assessment which asks individuals to rate questions related to physical, social/family, emotional, and functional well-being on a 5-point Likert Scale (0, not at all to 4, very much). Scores are summed across the items, resulting in a score from 0 to 148, with higher scores indicating better quality of life. Negative change scores indicate worse HRQOL with time.

Time frame:
From baseline to one month post-transplant
Reported as:
Mean · score on a scale
Change in Health-related Quality of Life Scores (Month 1)
score on a scaleInterventionControl
Change in Health-related Quality of Life Scores (Month 1)-7.53 ± 11.66-5.69 ± 11.59
SecondaryChange in Health-related Quality of Life Scores (Month 3)

HRQOL will be assessed using the Functional Assessment of Cancer Therapy - Bone Marrow Transplant (FACT-BMT). The FACT-BMT is a 47-item self-administered assessment which asks individuals to rate questions related to physical, social/family, emotional, and functional well-being on a 5-point Likert Scale (0, not at all to 4, very much). Scores are summed across the items, resulting in a score from 0 to 148, with higher scores indicating better quality of life. Negative change scores indicate worse HRQOL with time.

Time frame:
Baseline to three months post-transplant
Reported as:
Mean · score on a scale
Change in Health-related Quality of Life Scores (Month 3)
score on a scaleInterventionControl
Change in Health-related Quality of Life Scores (Month 3)-3.96 ± 9.11-1.43 ± 16.79
SecondaryChange in Health-related Quality of Life Scores (Month 6)

HRQOL will be assessed using the Functional Assessment of Cancer Therapy - Bone Marrow Transplant (FACT-BMT). The FACT-BMT is a 47-item self-administered assessment which asks individuals to rate questions related to physical, social/family, emotional, and functional well-being on a 5-point Likert Scale (0, not at all to 4, very much). Scores are summed across the items, resulting in a score from 0 to 148, with higher scores indicating better quality of life. Negative change scores indicate worse HRQOL with time.

Time frame:
Baseline to six months post-transplant
Reported as:
Mean · score on a scale
Change in Health-related Quality of Life Scores (Month 6)
score on a scaleInterventionControl
Change in Health-related Quality of Life Scores (Month 6)-4.36 ± 14.090.28 ± 12.17
SecondaryChange in Depression Scores (Month 1)

Depression will be assessed using the Patient Reported Outcomes Measurement Information System - Depression (PROMIS-D) 8a short form. Scores for all PROMIS measures are reported on the T-score metric in which the mean=50 and standard deviation (SD) = 10 are centered on the general population means. Higher scores represent greater degrees of mood symptoms. Positive change scores indicate worse mood over time.

Time frame:
Baseline to one month post-transplant
Reported as:
Mean · T-score
Change in Depression Scores (Month 1)
T-scoreInterventionControl
Change in Depression Scores (Month 1)-1.34 ± 8.281.16 ± 6.12
SecondaryChange in Depression Scores (Month 3)

Depression will be assessed using the Patient Reported Outcomes Measurement Information System - Depression (PROMIS-D) 8a short form. Scores for all PROMIS measures are reported on the T-score metric in which the mean=50 and standard deviation (SD) = 10 are centered on the general population means. Higher scores represent greater degrees of mood symptoms. Positive change scores indicate worse mood over time.

Time frame:
Baseline to three months post-transplant
Reported as:
Mean · T-score
Change in Depression Scores (Month 3)
T-scoreInterventionControl
Change in Depression Scores (Month 3)0.93 ± 6.240.32 ± 9.53
SecondaryChange in Depression Scores (Month 6)

Depression will be assessed using the Patient Reported Outcomes Measurement Information System - Depression (PROMIS-D) 8a short form. Scores for all PROMIS measures are reported on the T-score metric in which the mean=50 and standard deviation (SD) = 10 are centered on the general population means. Higher scores represent greater degrees of mood symptoms. Positive change scores indicate worse mood over time.

Time frame:
Baseline to six months post-transplant
Reported as:
Mean · T-score
Change in Depression Scores (Month 6)
T-scoreInterventionControl
Change in Depression Scores (Month 6)0.14 ± 6.88-1.66 ± 7.89
SecondaryChange in Post-traumatic Stress Symptom Scores (Month 1)

Post-traumatic stress symptoms will be measured using the Post Traumatic Stress Syndrome Scale 14 (PTSS-14). The PTSS-14 is a 14-item self-administered assessment. Questions are on a 7-point Likert-type Scale (1, never to 7, always) resulting in a total score between 14 and 98. Higher scores represent a more likely diagnosis of post-traumatic stress disorder (PTSD). Positive change scores indicate worse post-traumatic stress over time.

Time frame:
Baseline to one month post-transplant
Reported as:
Mean · score on a scale
Change in Post-traumatic Stress Symptom Scores (Month 1)
score on a scaleInterventionControl
Change in Post-traumatic Stress Symptom Scores (Month 1)-0.52 ± 10.881.55 ± 6.92
SecondaryChange in Post-traumatic Stress Symptom Scores (Month 3)

Post-traumatic stress symptoms will be measured using the Post Traumatic Stress Syndrome Scale 14 (PTSS-14). The PTSS-14 is a 14-item self-administered assessment. Questions are on a 7-point Likert-type Scale (1, never to 7, always) resulting in a total score between 14 and 98. Higher scores represent a more likely diagnosis of post-traumatic stress disorder (PTSD). Positive change scores indicate worse post-traumatic stress over time.

Time frame:
Baseline to three months post-transplant
Reported as:
Mean · score on a scale
Change in Post-traumatic Stress Symptom Scores (Month 3)
score on a scaleInterventionControl
Change in Post-traumatic Stress Symptom Scores (Month 3)-1.50 ± 6.580.83 ± 5.63
SecondaryChange in Post-traumatic Stress Symptom Scores (Month 6)

Post-traumatic stress symptoms will be measured using the Post Traumatic Stress Syndrome Scale 14 (PTSS-14). The PTSS-14 is a 14-item self-administered assessment. Questions are on a 7-point Likert-type Scale (1, never to 7, always) resulting in a total score between 14 and 98. Higher scores represent a more likely diagnosis of post-traumatic stress disorder (PTSD). Positive change scores indicate worse post-traumatic stress over time.

Time frame:
Baseline to six months post-transplant
Reported as:
Mean · score on a scale
Change in Post-traumatic Stress Symptom Scores (Month 6)
score on a scaleInterventionControl
Change in Post-traumatic Stress Symptom Scores (Month 6)1.79 ± 9.141.32 ± 7.00
SecondaryChange in Cognitive Function Scores (Month 1)

Cognitive function will be assessed using the Montreal Cognitive Assessment (MOCA). The MOCA is a clinician-administered tool with scores ranging from 0 to 30. Lower scores indicate worse cognitive function. Scores ≤ 25 are considered clinically significant. Positive change scores indicate better function with time.

Time frame:
From baseline to one month post-transplant
Reported as:
Mean · score on a scale
Change in Cognitive Function Scores (Month 1)
score on a scaleInterventionControl
Change in Cognitive Function Scores (Month 1)-0.70 ± 3.35-0.09 ± 2.76
SecondaryChange in Cognitive Function Scores (Month 3)

Cognitive function will be assessed using the Montreal Cognitive Assessment (MOCA). The MOCA is a clinician-administered tool with scores ranging from 0 to 30. Lower scores indicate worse cognitive function. Scores ≤ 25 are considered clinically significant. Positive change scores indicate better function with time.

Time frame:
Baseline to three months post-transplant
Reported as:
Mean · score on a scale
Change in Cognitive Function Scores (Month 3)
score on a scaleInterventionControl
Change in Cognitive Function Scores (Month 3)-0.12 ± 0.970.97 ± 2.82
SecondaryChange in Cognitive Function Scores (Month 6)

Cognitive function will be assessed using the Montreal Cognitive Assessment (MOCA). The MOCA is a clinician-administered tool with scores ranging from 0 to 30. Lower scores indicate worse cognitive function. Scores ≤ 25 are considered clinically significant. Positive change scores indicate better function with time.

Time frame:
From baseline to six months post-transplant
Reported as:
Mean · score on a scale
Change in Cognitive Function Scores (Month 6)
score on a scaleInterventionControl
Change in Cognitive Function Scores (Month 6)0.71 ± 3.321.54 ± 2.87
SecondaryChange in Functional Status Scores (Month 1)

Functional status will be measured using the Eastern Cooperative Oncology Group (ECOG) performance scale. ECOG performance status is a single question scored on a 6-point scale (range 0 to 5) with higher scores representing greater physical restriction due to illness. Negative change scores indicate better function with time.

Time frame:
Baseline to one month post-transplant
Reported as:
Mean · score on a scale
Change in Functional Status Scores (Month 1)
score on a scaleInterventionControl
Change in Functional Status Scores (Month 1)0.70 ± 0.670.88 ± 0.93
SecondaryChange in Functional Status Scores (Month 3)

Functional status will be measured using the Eastern Cooperative Oncology Group (ECOG) performance scale. ECOG performance status is a single question scored on a 6-point scale (range 0 to 5) with higher scores representing greater physical restriction due to illness. Negative change scores indicate better function with time.

Time frame:
From baseline to three months post-transplant
Reported as:
Mean · score on a scale
Change in Functional Status Scores (Month 3)
score on a scaleInterventionControl
Change in Functional Status Scores (Month 3)0.69 ± 0.620.60 ± 0.89
SecondaryChange in Functional Status Scores (Month 6)

Functional status will be measured using the Eastern Cooperative Oncology Group (ECOG) performance scale. ECOG performance status is a single question scored on a 6-point scale (range 0 to 5) with higher scores representing greater physical restriction due to illness. Negative change scores indicate better function with time.

Time frame:
Baseline to six months post-transplant
Reported as:
Mean · score on a scale
Change in Functional Status Scores (Month 6)
score on a scaleInterventionControl
Change in Functional Status Scores (Month 6)0.46 ± 0.930.21 ± 0.63

Adverse events

Collected over Adverse event (AE) data were only collected from October 2017 through February 2020, during the intervention phase of the study and coinciding with participants' hospitalization for hematopoietic stem cell transplantation. This phase lasted up to 30 days for each participant. The study was completed on August 10, 2020, as secondary outcomes were collected for an additional 5 months after completion of AE data collection.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Intervention1/30 (3.3%)0/30 (0%)0/30 (0%)
Control0/34 (0%)0/34 (0%)0/34 (0%)

Baseline characteristics

Only participants who met the following a priori criteria were counted: 1.) received all seven days of the treatment; 2.) received at least 17/21 (80%) scheduled study drug doses; and 3.) delirium was assessed at least weekly until the participant was found to be delirious, reached 30 days post-transplant, or was discharged.

Age, Continuous
Age, Continuous(years)InterventionControlTotal
Mean54.9 ± 12.553.6 ± 14.754.2 ± 13.6
Sex: Female, Male
Sex: Female, Male(Participants)InterventionControlTotal
Female111324
Male172037
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)InterventionControlTotal
Hispanic or Latino112
Not Hispanic or Latino273259
Unknown or Not Reported000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)InterventionControlTotal
American Indian or Alaska Native000
Asian000
Native Hawaiian or Other Pacific Islander000
Black or African American369
White252752
More than one race000
Unknown or Not Reported000
Region of Enrollment
Region of Enrollment(participants)InterventionControlTotal
United States283361
Education
Education(years)InterventionControlTotal
Mean14.7 ± 2.715.3 ± 2.715.0 ± 2.7
Diagnosis
Diagnosis(Participants)InterventionControlTotal
Acute leukemia181937
Chronic leukemia257
Lymphoma022
Myelodysplastic Syndrome5510
Myeloproliferative Disorder213
Other112
CIBMTR Disease Risk Index
CIBMTR Disease Risk Index(Participants)InterventionControlTotal
N/A336
low171936
intermediate3912
high527

3 further baseline measures are reported on the registry.

07

Study locations

1 site
  • University of North Carolina at Chapel Hill
    Chapel Hill, North Carolina 27514, United States
08

References and documents

Publications

  • Nakamura ZM, Deal AM, Park EM, Quillen LJ, Chien SA, Stanton KE, McCabe SD, Heiling HM, Wood WA, Shea TC, Rosenstein DL. A randomized double-blind placebo-controlled trial of intravenous thiamine for prevention of delirium following allogeneic hematopoietic stem cell transplantation. J Psychosom Res. 2021 Jul;146:110503. doi: 10.1016/j.jpsychores.2021.110503. Epub 2021 Apr 27. PubMed 33945982 ↗

Study documents

  • Protocol and statistical analysis plan · Mar 26, 2020

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

09

Registry details

Key details

Study ID
NCT03263442
Lead sponsor
UNC Lineberger Comprehensive Cancer Center
Collaborators
Rising Tide Foundation
Responsible party
Sponsor
First posted
Aug 28, 2017
Start date
Oct 16, 2017
Primary completion
Mar 2, 2020
Completion
Aug 10, 2020
Results posted
Apr 26, 2021
Last update
Oct 19, 2021

Study contacts

Donald Rosenstein, MD
study chair · University of North Carolina, Chapel Hill
Zev Nakamura, MD
principal investigator · University of North Carolina, Chapel Hill

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Sep 2021. You cannot join it, but the record below documents what was studied.

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