A Phase 2 interventional study of Erythropoietin and Saline in Bipolar Disorder, Cognitive Impairment and Unipolar Depression, sponsored by Lars Vedel Kessing. Completed at 1 site in Denmark. Open to participants aged 18 Years to 65 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2023-03-16.
Sponsored by Lars Vedel Kessing · Phase 2, Interventional, and Treatment
The present trial consists of 2 sub-studies that investigate important novel aspects of treatment with erythropoietin (EPO) on cognitive dysfunction in bipolar disorder (BD) and recurrent unipolar depressive disorder (UD) (defined as minimum 2 treatment-requiring depressive episodes). The aims of the trial are three-fold. We aim to investigate the effects of 12 weekly recombinant human EPO infusions on cognition in (i) healthy people with cognitive impairment (substudy 1) and (ii) patients with remitted BD or recurrent UD (substudy 2), and (iii) explore early treatment-associated neural activity changes that may predict subsequent cognitive improvement.
It is hypothesized that:
i. 12 weekly EPO infusions improve cognition in healthy first-degree relatives and remitted BD patients in comparison with saline.
ii. EPO vs. saline-treated participants will display early cognition-related neural activity in the frontal lobes, which will correlate with cognitive improvement.
This trial will include healthy people (sub-study 1) and patients with bipolar disorder or recurrent unipolar depressive disorder in partial or full remission (defined as a score of ≤14 on the Hamilton Depression Rating Scale 17-items and the Young Mania Rating Scale, respectively (sub-study 2) with objectively-verified cognitive dysfunction. Participants will be recruited from Psychiatric Centres in The Mental Health Services in the Capital Region of Denmark, consultant psychiatrists in the Capital Region of Denmark, as well as through advertisements on relevant websites.
The study design comprises 4 major assessments (baseline, week 3, week 13, and a 6 month follow-up after treatment completion) and weekly safety monitoring and study medication infusions during a 12 week treatment period. The baseline assessment is divided into 2 days, 1-3 days apart for practical reasons and to avoid attrition. On the first day of the baseline assessment, participants will perform an fMRI scan. On the second baseline day, participants complete an assessment comprising neuropsychological testing, verbal IQ assessment, and filling in questionnaires concerning subjective cognitive complaints, quality of life, level of functioning, and functional capacity, as well as mood symptom severity ratings. Functional capacity is assessed using a clinician-rated interview and a performance-based task. After 2 weeks of treatment (i.e., 2 doses of EPO or saline) an fMRI scan, neuropsychological testing, mood ratings, and questionnaires on subjective cognitive difficulties are repeated. After treatment completion (week 13) and at the 6 month follow-up, the neuropsychological tests, questionnaires concerning subjective cognitive complaints, quality of life, and functional capacity (self-reported and performance-based) are repeated. Sleep quantity and quality in the past three days is assessed before each of the 4 major assessment time point. Blood samples are collected at baseline, week 3 and 13 for assessment of potential blood-based biomarkers of pro-cognitive effects.
Pharma Consulting Group AB (www.pharmaconsultinggroup.com) has conducted block randomization for each sub-study group, stratified for gender and age (sub-study 1: \< or >=30 years; sub-study 2: \< or >=35 years). Power calculation was also carried out by Pharma Consulting Group based on findings from a previous RCT in our group assessing the effect of 8 weeks of EPO treatment on the same cognitive composite score. In this trial, the clinically relevant differential change between EPO and saline groups following 12 weeks of treatment is assumed to be at least 0.4 SD (corresponding to a moderate effect size) on the primary outcome with SD of the change of 0.5. Assuming a 10% drop-out rate, we plan to recruit up to n=58 for each sub-study to achieve complete data sets for n=52 participants per sub-study.
Data from the primary, secondary, and tertiary outcomes will be analyzed using Mixed Models Design and Intention to Treat (ITT) analyses. Functional MRI data are pre-processed and analyzed with FMRIB Expert Analysis Tool (FEAT) and the 'randomize' algorithm implemented in FSL (FMRIB Software Library; www.fmrib.ox.ac.uk/fsl). Functional MRI data is analysed using region of interest (ROI) analyses to assess potential differences in neural activity within the dorsal prefrontal cortex and the hippocampi between EPO and placebo groups after 2 weeks of treatment. Exploratory whole-brain analyses are conducted to assess treatment-related activity change in other brain regions. Any differences in neural activity between treatment groups are correlated with potential changes in the primary cognitive composite measure after 2 weeks of treatment (week 3) and after treatment completion (week 13). If this correlation is significant, multiple regression analyses will be performed with adjustment for mood symptoms, age, and gender to assess the potential predictive value of early neural activity change for potential pro-cognitive efficacy after 12 weeks of EPO treatment.
1,683 studies on the registry are indexed under Bipolar Disorder; 266 are open to participants now.
This study's enrollment of 103 is above the median of 64 across 1,279 interventional studies indexed under Bipolar Disorder.
Browse Bipolar Disorder studies →Lars Vedel Kessing is the lead sponsor of 3 studies on the registry; 1 is open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
ECG (electrocardiogram)
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
BMI (body mass index)
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
12 intravenous infusions of recombinant human erythropoietin (EPO)
Drug: Erythropoietin
12 intravenous infusions of saline (1 ml NaCl)
Drug: Saline
40.000 IU/ml Erythropoietin (Epoetin alpha; Eprex) diluted with 100 ml saline (0.9% NaCl) is administered 12 times as intravenous infusions over 15 minutes.
Also known as: Eprex, EPO
1 ml NaCl is administered 4 times as intravenous infusions over 15 minutes
Also known as: Placebo
Cognitive composite score
A cognitive composite based on an average of the Rey Auditory Verbal Learning Test (RAVLT), Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Coding, verbal fluency with the letter "D", WAIS-III Letter-Number Sequencing, Trail Making Test B (TMT B) and Rapid Visual Information Processing (RVP) from Cambridge Cognition (CANTAB).
Time frame: Change from baseline and week 13
Rapid Visual Information Processing (RVP) from Cambridge Cognition (CANTAB)
Neuropsychological test assessing sustained attention
Time frame: Baseline, two weeks of treatment, week 13, and 6-months follow-up
Functional Assessment Short Test
A semi-structured interview assessing level of functioning
Time frame: Baseline, week 13, and 6-months follow-up
Rey Auditory Verbal Learning Test
Neuropsychological test assessing verbal memory
Time frame: Baseline, two weeks of treatment, week 13, and 6-months follow-up
Trail Making Test Part A
Neuropsychological test assessing attention and processing speed
Time frame: Baseline, two weeks of treatment, week 13, and 6-months follow-up
Trail Making Test Part B
Neuropsychological test assessing executive functions
Time frame: Baseline, two weeks of treatment, week 13, and 6-months follow-up
Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Coding
Neuropsychological test assessing attention
Time frame: Baseline, two weeks of treatment, week 13, and 6-months follow-up
Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Digit Span
Neuropsychological test assessing executive functions
Time frame: Baseline, two weeks of treatment, week 13, and 6-months follow-up
WAIS-III Letter-Number Sequencing
Neuropsychological test assessing executive functions
Time frame: Baseline, two weeks of treatment, week 13, and 6-months follow-up
Verbal fluency with the letter "D" and 'S"
Neuropsychological test assessing executive functions
Time frame: Baseline, two weeks of treatment, week 13, and 6-months follow-up
One Touch Stockings of Cambridge
A computerized neuropsychological test assessing executive functions
Time frame: Baseline, two weeks of treatment, week 13, and 6-months follow-up
Spatial Working Memory (SWM) from Cambridge Cognition
Neuropsychological test assessing sustained attention
Time frame: Baseline, two weeks of treatment, week 13, and 6-months follow-up
Brief University of California, San Diego Performance-Based Skills Assessment-B
Objective, performance-based assessment of level of functioning
Time frame: Baseline, week 13, and 6-months follow-up
Sheehan Disability Scale
Visual analogue scale assessing level of functioning (i.e., the magnitude to which social, professional, and everyday life is impaired by symptoms). Each of the three subscale items have numerical scores that range from 0 to 10 with higher scores representing worse outcomes. These subscale items can be summed into a total dimensional measure reflecting global functional impairment with scores that range from 0 (no functional impairment at all) to 30 (severe functional impairment).
Time frame: Baseline, week 13, and 6-months follow-up
The Assessment of Quality of Life
Questionnaire on quality of life
Time frame: Baseline, week 13, and 6-months follow-up
World Health Organization Quality of Life
Questionnaire on quality of life
Time frame: Baseline, week 13, and 6-months follow-up
Cognitive Complaints in Bipolar Disorder Rating Assessment
Questionnaire on subjective cognitive complaints
Time frame: Baseline, week 13, and 6-months follow-up
Work and Social Adjustment Scale
Questionnaire on occupational functioning (work and social adjustment). The questionnaire consists of five subscale items with numerical scores that range from 0 (reflecting no impairment at all) to 8 (reflecting severe impairment). These subscale items can be summed into a total dimensional measure assessing global work and social adjustment with scores that range from 0 to 40 (with higher scores reflecting worse outcomes).
Time frame: Baseline, week 13, and 6-months follow-up
Plan to share: No
Ran from Jul 2017 to primary completion in Oct 2022, 62 months.
Of 42 non-industry phase 2 interventional studies under Bipolar Disorder, half reached primary completion within 49 months of starting (the median), counting those still running; a quarter within 21 and three quarters within 63. This study's 62 months is above that.
Counting every sponsor, half of 56 studies reached it within 33 months; a quarter within 20 and three quarters within 60.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Mar 2023. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Erythropoietin
Lars Vedel Kessing