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RecruitingNCT06322212Updated Mar 13, 2026

Type 2 Diabetes and Blood Brain Barrier Improvement

An Early Phase 1 interventional study of Thiamine and Placebo in Type2diabetes, sponsored by University of California, Los Angeles. Recruiting at 1 site in United States. Open to participants aged 40 Years to 65 Years. Per ClinicalTrials.gov, last updated 2026-03-13.

Sponsored by University of California, Los Angeles · Early Phase 1, Interventional, and Prevention

Phase
Early Phase 1
Study type
Interventional
Enrollment
52
Allocation
Randomized
Ages
40 Years to 65 Years
Sex
All
01

Study summary

The majority of T2DM adults show thiamine (vitamin B1) deficiency which may contribute to impaired function. This study will examine patients with T2DM through brain MRI scans, cognition assessments, blood tests, and questionnaires. Our goal is to see if a thiamine treatment (taking vitamin B1 capsules) can improve function. Patients will be asked to come to UCLA two times three months apart and each visit will last about 2.5-3 hours.

Read the detailed description

Type 2 diabetes mellitus (T2DM) makes up 90-95% of all diagnosed diabetes mellitus, and is a serious health issue in the United States.1 T2DM adults show significant mood and cognitive deficits, symptoms that are associated with higher morbidity and mortality, poor self-care, and decreased quality of life, and the condition is linked with early dementia and Alzheimer's disease. Brain structural changes emerge in T2DM adults in sites that exert major influence on cognition and mood functions, potentially resulting from impaired blood brain barrier function (BBB). However, it is unclear whether BBB function can be repaired in T2DM adults, reducing impaired cognition and mood functions and early risks of dementia and Alzheimer's disease in the condition.

Several pre-clinical studies suggest the possibility for BBB function repair, including low-cost thiamine intervention. Thiamine is an essential co-factor for carbohydrate metabolism and adequate or higher levels promote aerobic metabolism and reduce neural injury. In addition, reduced thiamine levels are shown contributing to impaired endothelial cell functions and higher doses of thiamine treatment improve endothelial functions. Thus, lower thiamine levels can contribute to neural, as well as endothelial cell dysfunctions, resulting to impaired BBB function. The majority of T2DM adults show thiamine deficiency, which may contribute to impaired BBB function, but it is unclear if the thiamine treatment can improve BBB function in T2DM adults. The investigators hypothesize that thiamine intervention (3-months) will reduce impaired BBB function and will improve cognition and mood functions in T2DM adults with thiamine treatment compared to non-treated T2DM adults.

In summary, the investigators propose that low-cost thiamine treatment for 3-months in T2DM adults will repair BBB dysfunction and improve mood and cognition functions. If studies successful, the findings from this clinical trial might serve as a novel and innovative treatment strategy to repair BBB function, affecting less cognition and mood function, and hence better outcomes in T2DM adults, as well as in other adult conditions with impaired BBB function. This R21 exploratory clinical trial study will provide required data regarding the benefits of a low-cost thiamine intervention that could be implemented on a large-scale clinical trial to repair BBB function in T2DM adults, as congruent to the National Institutes of Health mission, and thus, decrease early risks of dementia and Alzheimer's disease, reduce morbidity and mortality, and increase quality of life in this serious and common T2DM patient population.

02

Conditions studied

  • Type2diabetes

Browse trials for

Keywords

  • MRI
  • Thiamine Treatment
  • Thiamine Deficiency
  • Cognition Assessments
03

Who can participate

Ages eligible
40 Years to 65 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Diagnosed T2DM
  • Outpatient status
  • Able to lay flat for imaging

Exclusion criteria

Exclusion Criteria:

  • A previous history of stroke
  • Current in-take of thiamine
  • Known thiamine allergy
  • Seizure disorder
  • Head trauma
  • Myocardial infarction
  • Current pregnancy (if female)
  • Diagnosed neuropsychiatric disorders (clinical depression, schizophrenia, manic-depression)
  • Diagnosed dementia
  • Sleep disordered breathing
  • Airway or chest deformities that would interfere with breathing
  • Chronic obstructive pulmonary disease
  • Cystic fibrosis
  • Presence of brain mass lesions
  • Any history of drug abuse (e.g., cocaine, tobacco, or cannabis)
  • Renal failure (requiring dialysis)
  • All T2DM adults with metallic and electronic implants (phrenic or cardiac pacemakers; although some pacemakers and cardioverter defibrillators are safe at a low magnetic field, they are not safe at 3.0-Tesla scanner)
  • Non-removable insulin pump/glucose sensor
  • Braces
  • Body weight more than 300 pounds (weight and height will be used to calculate BMI to determine if the patient will fit in the scanner and stay within parameters of size restrictions of MRI scanner table)
  • Any other contraindications to MRI, such as claustrophobia, or metallic-based tattoos, as per MRI safety website suggestions, will also be excluded.
04

Study design

Phase
Early Phase 1
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Single (Participant)
Enrollment
52 participants (estimated)

Study arms

  • Experimental
    BBB function, cognition, and mood in T2DM adults with Thiamine treatment.

    Analyze BBB function, cognition, and mood in T2DM adults with Thiamine treatment and compare to the placebo group.

    Dietary Supplement: Thiamine

  • Placebo comparator
    BBB function, cognition, and mood in T2DM adults without Thiamine treatment.

    Analyze BBB function, cognition, and mood in T2DM adults without Thiamine treatment and compare to the Thiamine treatment group.

    Other: Placebo

Interventions

  • Dietary supplementThiamine

    Participants will be provided instruction to take one 500 mg capsule of Thiamine (Vitamin B1) each day in the morning for 3-months.

    Also known as: B1

  • OtherPlacebo

    Participants will be provided instruction to take one capsule (placebo) each day in the morning for 3-months.

    Also known as: inactive

05

What researchers measure

Primary outcomes

  1. Assess if BBB function has been repaired.

    Assess the function of the Blood Brain Barrier.

    Time frame: After 3 months

  2. Analyze blood serum S100β levels.

    Analyze blood serum S100β (marker of BBB integrity) levels to see if they have been reduced in thiamine treated T2DM adults over T2DM adults without thiamine treatment.

    Time frame: After 3 months

  3. Examine cognition in T2DM adults with thiamine treatment.

    The investigator will examine cognition using the Wide Range Assessment of Memory and Learning 2 (WRAML2) to see if T2DM adults with thiamine treatment show improved cognition over T2DM adults without thiamine treatment.

    Time frame: After 3 months

  4. Cognition assessment in T2DM adults after thiamine treatment.

    The investigator will assess cognition using the Montreal Cognitive Assessment (MoCA) to see if T2DM adults with thiamine treatment show improved cognition over T2DM adults without thiamine treatment.

    Time frame: After 3 months

  5. Examine depression in T2DM adults with thiamine treatment.

    The investigator will examine depression using using the Beck Depression Inventory II (BDI-II) to see if T2DM adults with thiamine treatment have an improvement in mood compared to T2DM adults without thiamine treatment.

    Time frame: After 3 months

  6. Assess anxiety in T2DM adults with thiamine treatment.

    The investigator will assess anxiety using using the Beck Anxiety Inventory (BAI) to see if T2DM adults with thiamine treatment have an improvement in mood compared to T2DM adults without thiamine treatment.

    Time frame: After 3 months

06

Study locations

1 of 1 sites recruiting
  • UCLA
    Los Angeles, California 90095, United States
    Recruiting
07

References and documents

Publications

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  • Pike, N.A., Woo, M.A., Poulsen, M.K., Halnon, N.J., Lewis, A.B. & Kumar, R. Cognitive impairment in adolescents with congenital heart disease. American Heart Association Annual Meeting, November 15-19, Chicago, IL: 2014.
  • Hollingshead, A.B. Four factor index of social status. New Haven, CT: Yale University Press: 1975.
  • Wiley KD, Singh J. Vitamin B1 (Thiamine) Deficiency. 2026 Jan 31. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan-. Available from http://www.ncbi.nlm.nih.gov/books/NBK537204/ PubMed 30725889 ↗
  • Sullivan EV, Fama R. Wernicke's encephalopathy and Korsakoff's syndrome revisited. Neuropsychol Rev. 2012 Jun;22(2):69-71. doi: 10.1007/s11065-012-9205-2. Epub 2012 May 16. No abstract available. PubMed 22588370 ↗
  • Thomson, A.D., Guerrini, I. & Marshall, E.J. Wernicke's encephalopathy: role of thiamine. Pract Gastroenterol 33: 21-30, 2009.
  • Crook, M.A. Chapter 6 - Methods for assessment of Thiamine (Vitamin B1). In: Harrington D, editor. Laboratory Assessment of Vitamin Status: Academic Press; 2019. p. 149-64.
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Study documents

  • Protocol and informed consent form · Nov 17, 2023

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

Individual participant data

Plan to share: Yes — The investigator will make every effort to publish data in a timely manner. Once the findings related to changes in blood brain barrier based on brain MRI data before and after thiamine intervention have been published or by the end of award performance period, whichever is sooner, the MRI data, demographics, mood and cognition, and clinical data (devoid of individual identifiers) will be deposited in NIH supported domain-specific data sharing repository (NIMH Data Archive). All data will be labeled with consistent unique identifiers that will make it easily findable in data repository to interested research investigators. Data will be available forever after sharing with data repository to other investigators for secondary analyses.

Supporting information: Csr

08

Registry details

Key details

Study ID
NCT06322212
Lead sponsor
University of California, Los Angeles
Collaborators
National Institute on Aging (NIA)
Responsible party
Rajesh Kumar, PhD (Professor of Anesthesiology and Radiological Sciences, University of California, Los Angeles) — Principal investigator
First posted
Mar 20, 2024
Start date
Aug 1, 2024
Primary completion
Dec 31, 2026 (estimated)
Completion
Mar 31, 2027 (estimated)
Last update
Mar 13, 2026

Study contacts

Rajesh Kumar, PhD
Contact
rkumar@mednet.ucla.edu
310-206-1699
Dineth R Karunamuni, MS
Contact
dkarunamuni@mednet.ucla.edu
856-701-5332

Oversight

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

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