Thiamine DeficiencyNCT05480943
Prevalence of Thiamine Deficiency in Hospitalized Non-Alcoholic Veterans
An observational study of Thiamine Deficiency and Thiamine Deficiency; Sequelae, run by VA Office of Research and Development at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Thiamine Deficiency, Thiamine Deficiency; Sequelae
- What is being tested?
- Thiamine repletion
- How many people
- 206 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Jul 2022to 30 Dec 2024
- Phase
- Observational
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: 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.
Who may be able to join
- full admission to the hospital medical service (not on observation status)
Who cannot join
- excess alcohol intake as defined by the National Institute of Alcohol Abuse and Alcoholism
- taking thiamine supplement
- quadriplegic
- lives more than 75 miles from the medical center
- unable to demonstrate capacity to understand the study and provide informed consent
Trial locations and contacts
1 site in 1 country.
United States1 site
VA Sierra Nevada Health Care System, Reno, NV
Reno, Nevada, 89502-0993
About this study
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.
Read the detailed description
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.
- Conditions
- Thiamine Deficiency, Thiamine Deficiency; Sequelae
- Being tested
- Thiamine repletion
- Keywords
- thiamine deficiency, Wernicke's encephalopathy, beriberi, delirium, polyneuropathy, vitamin B1, falls
- Medical subject headings
- Thiamine Deficiency, Wernicke Encephalopathy, Beriberi, Delirium, Polyneuropathies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Thiamine repletionDietary supplement
If a participant is determined by clinical characteristics or biomarker results to be thiamine deficient, thiamine supplementation was provided.
| Study group | Role | What they receive |
|---|---|---|
| Hospitalized non-alcoholic Veterans | Any Veteran with full admission to the VA Sierra Nevada Healthcare System Hospital. Receives: Dietary Supplement: Thiamine repletion |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline
Secondary outcomes (2)
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.
Measured: 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.
Measured: Follow up at 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jul 2022
- Study start19 Jul 2022
- Primary completion30 Sep 2024
- Study completion30 Dec 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Thiamine DeficiencyStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Other
- Time perspective
- Prospective
- Enrolment
- 206 participants (actual)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Collaborators
- VA Sierra Nevada Health Care System
- Responsible party
- Sponsor
- Investigators
- Elisabeth A Mates, MD PhD, Principal investigator, VA Sierra Nevada Health Care System, Reno, NV
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05480943
- Sponsor's protocol ID
- F4101-P
- Other IDs
- IRBNet ID 1867369-3
- Status last verified
- Jul 2026
- First submitted
- 27 Jul 2022
- Last updated
- 12 Aug 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Deidentified data set will be shared upon request made to Dr. Elisabeth Mates
Publications
Mates E, Alluri D, Artis T, Riddle MS. A Retrospective Case Series of Thiamine Deficiency in Non-Alcoholic Hospitalized Veterans: An Important Cause of Delirium and Falling? J Clin Med. 2021 Apr 1;10(7):1449. doi: 10.3390/jcm10071449.
PubMed 33916273Gomes F, Bergeron G, Bourassa MW, Fischer PR. Thiamine deficiency unrelated to alcohol consumption in high-income countries: a literature review. Ann N Y Acad Sci. 2021 Aug;1498(1):46-56. doi: 10.1111/nyas.14569. Epub 2021 Feb 11.
PubMed 33576090Donnino MW, Carney E, Cocchi MN, Barbash I, Chase M, Joyce N, Chou PP, Ngo L. Thiamine deficiency in critically ill patients with sepsis. J Crit Care. 2010 Dec;25(4):576-81. doi: 10.1016/j.jcrc.2010.03.003. Epub 2010 Jun 19.
PubMed 20646908Whitfield KC, Bourassa MW, Adamolekun B, Bergeron G, Bettendorff L, Brown KH, Cox L, Fattal-Valevski A, Fischer PR, Frank EL, Hiffler L, Hlaing LM, Jefferds ME, Kapner H, Kounnavong S, Mousavi MPS, Roth DE, Tsaloglou MN, Wieringa F, Combs GF Jr. Thiamine deficiency disorders: diagnosis, prevalence, and a roadmap for global control programs. Ann N Y Acad Sci. 2018 Oct;1430(1):3-43. doi: 10.1111/nyas.13919. Epub 2018 Aug 27.
PubMed 30151974Lee DC, Chu J, Satz W, Silbergleit R. Low plasma thiamine levels in elder patients admitted through the emergency department. Acad Emerg Med. 2000 Oct;7(10):1156-9. doi: 10.1111/j.1553-2712.2000.tb01268.x.
PubMed 11015250Smith TJ, Johnson CR, Koshy R, Hess SY, Qureshi UA, Mynak ML, Fischer PR. Thiamine deficiency disorders: a clinical perspective. Ann N Y Acad Sci. 2021 Aug;1498(1):9-28. doi: 10.1111/nyas.14536. Epub 2020 Dec 10.
PubMed 33305487
Study at a glance
From the registry record, last updated by the sponsor on 12 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prevalence of Thiamine Deficiency in Hospitalized Non-Alcoholic Veterans
- ClinicalTrials.gov ID
- NCT05480943
- Acronym / sponsor ID
- F4101-P
- Conditions
- Thiamine Deficiency, Thiamine Deficiency; Sequelae
- Keywords
- thiamine deficiency, Wernicke's encephalopathy, beriberi, delirium, polyneuropathy, vitamin B1, falls
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 206 participants (actual)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Collaborators
- VA Sierra Nevada Health Care System
- Study start
- 19 Jul 2022 (actual)
- Primary completion
- 30 Sep 2024 (actual)
- Study completion
- 30 Dec 2024 (actual)
- First posted
- 29 Jul 2022 (actual)
- Results
- Posted 15 Oct 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Observational model
- Other
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Hospitalized non-alcoholic Veterans | – | Dietary Supplement: Thiamine repletionAny Veteran with full admission to the VA Sierra Nevada Healthcare System Hospital. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- 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.
Key inclusion criteria (1 listed)
- full admission to the hospital medical service (not on observation status)
Key exclusion criteria (5 listed)
- excess alcohol intake as defined by the National Institute of Alcohol Abuse and Alcoholism
- taking thiamine supplement
- quadriplegic
- lives more than 75 miles from the medical center
- unable to demonstrate capacity to understand the study and provide informed consent
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Thiamine repletionIf a participant is determined by clinical characteristics or biomarker results to be thiamine deficient, thiamine supplementation was provided. | Dietary supplement | Hospitalized non-alcoholic Veterans |
Primary outcome
Percentage of Participants With Thiamine Deficiency (Low Plasma Thiamine) Out of Total Number of Enrolled Veterans With Plasma Thiamine Results
Time frame: Baseline
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.
2 secondary outcomes
Association of Thiamine Deficiency and 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
Time frame: Follow up at 4 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Aug 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 33916273Mates E, Alluri D, Artis T, Riddle MS. A Retrospective Case Series of Thiamine Deficiency in Non-Alcoholic Hospitalized Veterans: An Important Cause of Delirium and Falling? J Clin Med. 2021 Apr 1;10(7):1449. doi: 10.3390/jcm10071449.
- Background: PubMed 33576090Gomes F, Bergeron G, Bourassa MW, Fischer PR. Thiamine deficiency unrelated to alcohol consumption in high-income countries: a literature review. Ann N Y Acad Sci. 2021 Aug;1498(1):46-56. doi: 10.1111/nyas.14569. Epub 2021 Feb 11.
- Background: PubMed 20646908Donnino MW, Carney E, Cocchi MN, Barbash I, Chase M, Joyce N, Chou PP, Ngo L. Thiamine deficiency in critically ill patients with sepsis. J Crit Care. 2010 Dec;25(4):576-81. doi: 10.1016/j.jcrc.2010.03.003. Epub 2010 Jun 19.
- Background: PubMed 30151974Whitfield KC, Bourassa MW, Adamolekun B, Bergeron G, Bettendorff L, Brown KH, Cox L, Fattal-Valevski A, Fischer PR, Frank EL, Hiffler L, Hlaing LM, Jefferds ME, Kapner H, Kounnavong S, Mousavi MPS, Roth DE, Tsaloglou MN, Wieringa F, Combs GF Jr. Thiamine deficiency disorders: diagnosis, prevalence, and a roadmap for global control programs. Ann N Y Acad Sci. 2018 Oct;1430(1):3-43. doi: 10.1111/nyas.13919. Epub 2018 Aug 27.
- Background: PubMed 11015250Lee DC, Chu J, Satz W, Silbergleit R. Low plasma thiamine levels in elder patients admitted through the emergency department. Acad Emerg Med. 2000 Oct;7(10):1156-9. doi: 10.1111/j.1553-2712.2000.tb01268.x.
- Background: PubMed 33305487Smith TJ, Johnson CR, Koshy R, Hess SY, Qureshi UA, Mynak ML, Fischer PR. Thiamine deficiency disorders: a clinical perspective. Ann N Y Acad Sci. 2021 Aug;1498(1):9-28. doi: 10.1111/nyas.14536. Epub 2020 Dec 10.
- Individual participant dataSharing planned: No. Deidentified data set will be shared upon request made to Dr. Elisabeth Mates
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Elisabeth A Mates, MD PhD principal investigator
VA Sierra Nevada Health Care System, Reno, NV
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Thiamine Deficiency and Thiamine Deficiency; Sequelae, run by VA Office of Research and Development at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Oct 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With Thiamine Deficiency (Low Plasma Thiamine) Out of Total Number of Enrolled Veterans With Plasma Thiamine Results (time frame: Baseline). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05480943, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Aug 2026.