Type 2 Diabetes and Blood Brain Barrier Improvement

Официальное название

Type 2 Diabetes Mellitus and Blood Brain Barrier Improvement - A Randomized Clinical Trial

Обзор

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.

Подробное описание

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.

Вмешательства

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

Первичные конечные точки

• Assess if BBB function has been repaired. [Срок оценки: After 3 months]
• Analyze blood serum S100β levels. [Срок оценки: After 3 months]
• Examine cognition in T2DM adults with thiamine treatment. [Срок оценки: After 3 months]
• Cognition assessment in T2DM adults after thiamine treatment. [Срок оценки: After 3 months]
• Examine depression in T2DM adults with thiamine treatment. [Срок оценки: After 3 months]
• Assess anxiety in T2DM adults with thiamine treatment. [Срок оценки: After 3 months]

Критерии участия

Критерии включения

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

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Профилактика

Центры проведения

США · 1 центр

• UCLA — Los Angeles

Публикации

• Umegaki H. Type 2 diabetes as a risk factor for cognitive impairment: current insights. Clin Interv Aging. 2014 Jun 28;9:1011-9. doi: 10.2147/CIA.S48926. eCollection 2014. PMID 25061284
• Vincent C, Hall PA. Executive Function in Adults With Type 2 Diabetes: A Meta-Analytic Review. Psychosom Med. 2015 Jul-Aug;77(6):631-42. doi: 10.1097/PSY.0000000000000103. PMID 25469685
• Nooyens AC, Baan CA, Spijkerman AM, Verschuren WM. Type 2 diabetes and cognitive decline in middle-aged men and women: the Doetinchem Cohort Study. Diabetes Care. 2010 Sep;33(9):1964-9. doi: 10.2337/dc09-2038. Epub 2010 Jun 2. PMID 20519662
• Spauwen PJ, Kohler S, Verhey FR, Stehouwer CD, van Boxtel MP. Effects of type 2 diabetes on 12-year cognitive change: results from the Maastricht Aging Study. Diabetes Care. 2013 Jun;36(6):1554-61. doi: 10.2337/dc12-0746. Epub 2012 Dec 28. PMID 23275366
• Worrall G, Moulton N, Briffett E. Effect of type II diabetes mellitus on cognitive function. J Fam Pract. 1993 Jun;36(6):639-43. PMID 8505607
• Lowe LP, Tranel D, Wallace RB, Welty TK. Type II diabetes and cognitive function. A population-based study of Native Americans. Diabetes Care. 1994 Aug;17(8):891-6. doi: 10.2337/diacare.17.8.891. PMID 7956638
• Dey J, Misra A, Desai NG, Mahapatra AK, Padma MV. Cognitive function in younger type II diabetes. Diabetes Care. 1997 Jan;20(1):32-5. doi: 10.2337/diacare.20.1.32. PMID 9028690
• McGuire LC, Ford ES, Ajani UA. The impact of cognitive functioning on mortality and the development of functional disability in older adults with diabetes: the second longitudinal study on aging. BMC Geriatr. 2006 May 1;6:8. doi: 10.1186/1471-2318-6-8. PMID 16650284

Идентификаторы

NCT: NCT06322212 · 23-001083 · 1R21AG085268-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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