Type 2 Diabetes and Blood Brain Barrier Improvement
- Conditions
- Type2diabetes
- Interventions
- Dietary Supplement: ThiamineOther: Placebo
- Registration Number
- NCT06322212
- Lead Sponsor
- University of California, Los Angeles
- Brief 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.
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 52
- Diagnosed T2DM
- Outpatient status
- Able to lay flat for imaging
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description BBB function, cognition, and mood in T2DM adults with Thiamine treatment. Thiamine Analyze BBB function, cognition, and mood in T2DM adults with Thiamine treatment and compare to the placebo group. BBB function, cognition, and mood in T2DM adults without Thiamine treatment. Placebo Analyze BBB function, cognition, and mood in T2DM adults without Thiamine treatment and compare to the Thiamine treatment group.
- Primary Outcome Measures
Name Time Method Cognition assessment in T2DM adults after thiamine treatment. After 3 months 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.
Analyze blood serum S100β levels. After 3 months 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.
Examine cognition in T2DM adults with thiamine treatment. After 3 months 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.
Examine depression in T2DM adults with thiamine treatment. After 3 months 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.
Assess anxiety in T2DM adults with thiamine treatment. After 3 months 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.
Assess if BBB function has been repaired. After 3 months Assess the function of the Blood Brain Barrier.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
UCLA
🇺🇸Los Angeles, California, United States