Type 2 Diabetes and Blood Brain Barrier Improvement

University of California, Los Angeles (UCLA)

Status and phase

Enrolling

Early Phase 1

Conditions

Type2diabetes

Treatments

Other: Placebo

Dietary Supplement: Thiamine

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT06322212

23-001083

1R21AG085268-01 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment

52 estimated patients

Sex

All

Ages

40 to 65 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Diagnosed T2DM
Outpatient status
Able to lay flat for imaging

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.