An observational study in Thiamine Deficiency and Thiamine Deficiency; Sequelae, sponsored by VA Office of Research and Development. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-08-12.
Sponsored by VA Office of Research and Development · Observational
Thiamine micronutrient deficiency (TD) can cause a variety of non-specific symptoms and leads to several thiamine deficiency disorders such as heart failure, polyneuropathy, Wernicke's Encephalopathy and generalized weakness and debility. Symptoms are often vague and non-specific such as fatigue, leg swelling, imbalance, confusion, mood disorders, gastrointestinal upset, and weakness. Hospitalized Veterans may be particularly susceptible to TD due to food insecurity and chronic illnesses which cause inflammation and increased metabolic demands. This study aims to determine the prevalence of TD in hospitalized Veterans which has never been done before. The investigators also seek to identify risk factors causing TD including acute and chronic forms of inflammation, food insecurity, and dietary habits. Lastly, the investigators hope to clarify the abnormally low levels of blood thiamine that correlate with symptoms of TD that improve with replenishment.
Background: Thiamine deficiency (TD) causes a variety of thiamine deficiency disorders (TDDs) such as neuropsychiatric disturbances, polyneuropathy, ataxia, weakness and falling, and non-ischemic heart failure. Left untreated, TD can be associated with poor quality of life, loss of independence, and inability to complete activities of daily living. The prevalence of TD in non-alcohol using hospitalized Veterans is not known but is probably much higher than the general population. Loss of functional ability leads to increased need for rehabilitation.
The objective of this proposal is to measure the prevalence of TDDs in Veterans who do not use excess alcohol who are ill enough to require hospitalization, determine if inflammation increases the risk of developing TD, and determine the optimal cutoff points for two biomarkers of TD to diagnose of TDDs. The central hypothesis is that TD prevalence is as high as 25% in hospitalized non-alcoholic Veterans, far greater than the historically reported prevalence of 3% or less, and that TDD's occur in the "low normal" range of current cutoff values for available thiamine bioassays. A secondary hypothesis is that inflammatory conditions, which are known to cause cachexia and malnutrition, put hospitalized Veterans at increased risk as they often present with acute inflammatory conditions. The rationale underlying this proposal is that hospital practitioners currently underdiagnose and undertreat TDDs which leads to continued morbidity and loss of function. If the hypothesis is correct that the prevalence is as high as 25%, this knowledge will increase awareness of the problem and lead practitioners to diagnose and treat them more often. In addition, clarifying the "abnormally low" biomarker cutoff levels by measuring them in Veterans with TDDs is very important as the current "normal" ranges were determined in healthy volunteers. The central hypothesis will be tested by pursuing three specific aims: 1) determine the prevalence of TD, as defined by whole blood and plasma thiamine levels together with symptom responsive disease in consecutively hospitalized medicine patients who do not use excessive alcohol; 2) define TDDs as cases with low or "low normal" thiamine levels and symptoms that improve with thiamine replenishment; 3) determine if acute and chronic inflammatory conditions with elevated biomarkers of inflammation increase the risk of developing TDD. The investigators expect to find the prevalence of TD is closer to 25% and that the low end of "normal" biomarker levels as published by reference laboratories is too low, missing a percentage of TDDs.
Research design: To accomplish these aims, the investigators will utilize a prospective cohort study design to determine the prevalence of TD in consecutively hospitalized non-alcoholic medicine patients, as defined by low or "low normal" thiamine biomarker levels and thiamine responsive symptoms. Nested within this the investigators will conduct an open label treatment study with those exhibiting symptoms and define TDDs as cases with low or "low normal" thiamine levels and symptoms of TD that improve with thiamine administration. Lastly, utilizing a nested case control study design with cases being those with a TDD and controls being asymptomatic Veterans with normal biomarkers, determine if acute and chronic inflammatory conditions with elevated biomarkers of inflammation increase the risk of developing TDDs.
18 studies on the registry are indexed under Thiamine Deficiency; 1 is open to participants now.
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Veterans who are admitted to the medicine service at the VA Sierra Nevada Healthcare System hospital in Reno, NV who do not use alcohol to excess. The Veterans will need to live within 75 miles of the medical center to facilitate return for follow up appointments.
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.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Any Veteran with full admission to the VA Sierra Nevada Healthcare System Hospital.
Dietary Supplement: Thiamine repletion
If a participant is determined by clinical characteristics or biomarker results to be thiamine deficient, thiamine supplementation was provided.
Percentage of Participants With Thiamine Deficiency (Low Plasma Thiamine) Out of Total Number of Enrolled Veterans With Plasma Thiamine Results
The percentage of enrolled non-alcoholic veterans who have thiamine deficiency (defined as low plasma thiamine levels) out of the total number of enrolled Veterans with plasma thiamine results.
Time frame: Baseline
Association of Thiamine Deficiency and Inflammation
Determine if there is an association between thiamine deficiency defined by low plasma thiamine levels, and elevated highly sensitive C-reactive protein indicating inflammation.
Time frame: Baseline
Cut Point Analysis of Plasma Thiamine Concentration (Nanomoles/Liter) Below Which Most Participants Composite Thiamine Deficiency Symptom Score Improved With Thiamine Repletion
Thiamine deficiency symptoms and physical exam findings of ophthalmoplegia, muscle weakness, and ataxia received a score before thiamine repletion and after. Each component was scaled equally and combined into a composite score before and after treatment. The investigators used receiver operator characteristic analysis to find the value of plasma thiamine concentration below which most individuals improved with specificity of 0.5 or higher. The resulting analysis showed the value of plasma thiamine in nmol/L resulting in a specificity of 0.5 or higher which was determined to be the optimal cut point of plasma thiamine concentration to identify individuals with clinically relevant thiamine deficiency.
Time frame: Follow up at 4 weeks
All admissions to the hospital were screened and Veterans were excluded if they reported excess alcohol intake; taking thiamine; lived more than 70 miles from the hospital. Those who passed screening were approached for consent. If they were unable to comprehend and "read back" basic elements of the informed consent (as determined by the U-ARE protocol), they were not included due to prohibitive state laws. The first patient was enrolled on July 19, 2022. The last Veteran was enrolled 8/27/2024.
| Milestone | Veterans Without Alcohol Use Disorder Admitted to the Hospital |
|---|---|
| Started | 206 |
| Obtained plasma thiamine results | 181 |
| Answered interview questions | 177 |
| Completed initial physical exam | 162 |
| Completed | 162 |
| Not completed | 44 |
| Withdrew: Lost to follow-up | 31 |
| Withdrew: Protocol violation | 12 |
| Withdrew: Withdrawal by subject | 1 |
| Milestone | Veterans Without Alcohol Use Disorder Admitted to the Hospital |
|---|---|
| Started | 124 |
| Completed | 60 |
| Not completed | 64 |
| Withdrew: Lost to follow-up | 64 |
The percentage of enrolled non-alcoholic veterans who have thiamine deficiency (defined as low plasma thiamine levels) out of the total number of enrolled Veterans with plasma thiamine results.
| Participants | Enrolled Veterans With Plasma Thiamine Results |
|---|---|
| Percentage of Participants With Thiamine Deficiency (Low Plasma Thiamine) Out of Total Number of Enrolled Veterans With Plasma Thiamine Results | 49 |
Determine if there is an association between thiamine deficiency defined by low plasma thiamine levels, and elevated highly sensitive C-reactive protein indicating inflammation.
| Participants | Enrolled Veterans With Both Plasma Thiamine and CRP Results Who Were Thiamine Deficient |
|---|---|
| Normal CRP | 8 |
| Elevated CRP | 25 |
Thiamine deficiency symptoms and physical exam findings of ophthalmoplegia, muscle weakness, and ataxia received a score before thiamine repletion and after. Each component was scaled equally and combined into a composite score before and after treatment. The investigators used receiver operator characteristic analysis to find the value of plasma thiamine concentration below which most individuals improved with specificity of 0.5 or higher. The resulting analysis showed the value of plasma thiamine in nmol/L resulting in a specificity of 0.5 or higher which was determined to be the optimal cut point of plasma thiamine concentration to identify individuals with clinically relevant thiamine deficiency.
| nanomoles/liter | Cut Point Analysis of Thiamine Biomarker |
|---|---|
| Cut Point Analysis of Plasma Thiamine Concentration (Nanomoles/Liter) Below Which Most Participants Composite Thiamine Deficiency Symptom Score Improved With Thiamine Repletion | 8.5 |
Collected over two months. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Hospitalized Non-alcoholic Veterans | 23/181 (12.7%) | 0/181 (0%) | 1/181 (0.6%) |
| Event | Hospitalized Non-alcoholic Veterans |
|---|---|
| DiarrheaGastrointestinal disorders | 1/181 |
| Age, Continuous(years) | Hospitalized Non-alcoholic Veterans |
|---|---|
| Mean | 70.33 ± 11.53 |
| Sex: Female, Male(Participants) | Hospitalized Non-alcoholic Veterans |
|---|---|
| Female | 10 |
| Male | 196 |
| Ethnicity (NIH/OMB)(Participants) | Hospitalized Non-alcoholic Veterans |
|---|---|
| Hispanic or Latino | 6 |
| Not Hispanic or Latino | 193 |
| Unknown or Not Reported | 7 |
| Race (NIH/OMB)(Participants) | Hospitalized Non-alcoholic Veterans |
|---|---|
| American Indian or Alaska Native | 5 |
| Asian | 2 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 11 |
| White | 175 |
| More than one race | 1 |
| Unknown or Not Reported | 12 |
| Region of Enrollment(Participants) | Hospitalized Non-alcoholic Veterans |
|---|---|
| United States | 206 |
| Plasma thiamine level(Participants) | Hospitalized Non-alcoholic Veterans |
|---|---|
| Low plasma thiamine | 49 |
| Normal plasma thiamine | 132 |
| Highly sensitive C-reactive protein(Participants) | Hospitalized Non-alcoholic Veterans |
|---|---|
| Normal C-reactive protein | 38 |
| Elevated C-reactive protein | 87 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: No — Deidentified data set will be shared upon request made to Dr. Elisabeth Mates
This study is completed, as verified in Jul 2026. You cannot join it, but the record below documents what was studied.
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