Clinical trial NCT02416193: Can Vitamin D3 Improve Cognitive Function in Individuals With Type 2 Diabetes? (THINK-D)
Official title: Can Vitamin D3 Improve Cognitive Function in Individuals With Type 2 Diabetes? (THINK-D)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Diabetes
Executive Dysfunction
Keywords: Diabetes
Cognition
Functioning
Lead sponsor: Loyola University
Sponsor class: OTHER
Collaborators: name: University of Chicago
First posted: 2015-04-14
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Diabetes increases the risk of cognitive dysfunction. The incidence of dementia is 1.5 to 2.5 times higher in persons with diabetes than the general population. There is evidence that cognitive decline significantly impacts the ability to self-manage diabetes. Strategies to prevent cognitive decline in persons with diabetes has not been well studied. A recent study reported that in persons who had vitamin D deficiency, the risk for all-cause dementia and Alzheimer's was doubled. Vitamin D receptors are located in the brain and deficiency of vitamin D has been reported to negatively affect the development of brain. Therefore, providing vitamin D supplementation to improve cognitive function is worthy of study. The investigators propose a small, randomized controlled trial to determine the effects of vitamin D3 supplementation in persons with type 2 diabetes who have symptoms of cognitive impairment. Persons will be randomized to receive either weekly vitamin D3 supplementation (50,000 IUs) or a matching comparator (5000 IUs) for a period of three months. The study aims are to determine (1) the effect of vitamin D3 supplementation on cognitive function and (2) the effect of vitamin D3 supplementation on diabetes self-management. A sample of persons with type 2 diabetes (n=62), who have a subjective complaint of a cognitive dysfunction or scoring at least one standard deviation below normal on a cognitive functioning screening test, have vitamin D levels less 30 ng/ml, are not depressed (as this impacts cognitive function), and do not have severe diabetes complication will be recruited. Participants will be phone screened and complete two baseline visits prior to randomization. They will then have phone call and follow-up visits to assess (1) cognitive function using standardized tests to assess for executive function (2) serum measurements (HBA1c, fasting glucose, vitamin D levels, and cardiometabolic profile) and (3) surveys to assess cognitive function as well as self-management behaviors.

Detailed description: Study Aims Diabetes increases the risk of cognitive dysfunction. The incidence of dementia is 1.5 to 2.5 times higher in persons with diabetes than the general population (1). There is evidence that cognitive decline significantly impacts the ability to self-manage diabetes (2). Strategies to prevent cognitive decline in persons with diabetes has not been well studied. A recent study reported that in persons who had vitamin D deficiency, the risk for all-cause dementia and Alzheimer's was doubled (3). Vitamin D receptors are located in the brain, and deficiency of vitamin D has been reported to negatively affect the development of brain and impact both growth factor signaling and neural activity (4, 5). Therefore, providing vitamin D supplementation to improve cognitive function in persons with diabetes who are at great risk for this comorbid condition is important. The investigators propose a small, randomized controlled trial to determine the effects of vitamin D3 supplementation in persons with type 2 diabetes who have symptoms of cognitive impairment. Persons will be randomized to receive either weekly vitamin D3 supplementation (50,000 IUs) or a matching comparator (5000 IUs) for a period of three months.

Primary Aim: To determine the effect of vitamin D3 supplementation on cognitive function for persons with type 2 diabetes.

Primary Hypothesis: Persons receiving weekly vitamin D3 supplementation (50,000 IUs) will have improved cognitive function compared to those receiving the comparator (5000 IUs) at three months.

Secondary Aim: To determine the effect of vitamin D3 supplementation on diabetes self-management.

Secondary Hypothesis: Persons receiving weekly vitamin D3 supplementation (50,000 IUs) will have improved self-management compared to those receiving the comparator (5000 IUs) at three months.

The importance of this study is several fold. Vitamin D supplementation is a low cost intervention (6), it has minimal side effects (7), and it could have high impact for persons with type 2 diabetes who suffer from cognitive impairment which can significantly affect their diabetes self-management.

Eligibility criteria: Inclusion Criteria:

* Women and men aged 18 to 75 years
* Have type 2 diabetes
* Having a subjective complaint of a cognitive dysfunction or scoring at least one standard deviation below normal on a cognitive functioning screening test
* Vitamin D level as measured by 25-hydroxyvitamin D (25-OH D) \< 32 ng/mL
* Under the care of a healthcare provider
* Systolic blood pressure ≤160 and diastolic blood pressure ≤100

Exclusion Criteria:

* Persons with malabsorption problems (e.g., crohn's disease)
* Hypercalcemia
* Supplementation other than a daily multivitamin
* Severe complications of diabetes (i.e., amputation, blindness, and dialysis)
* Concomitant use of steroids
* GFR \< 60
* Creatinine \> 1.2
* Significant depressive symptoms
* Having a history of bipolar depression, psychotic disorders, loss of consciousness greater than 5 minutes, or a current alcohol or substance use disorder
* Other serious medical conditions deemed significant by the PI or medical monitor
* Concomitant use of cholinesterase inhibitors
* Concomitant use of anxiolytics, kava kava, St. John's Wort, or Ginkgo Biloba
* Pregnancy
* HbA1c \>13%

Primary outcomes:
measure: Letter-Number Sequencing
timeFrame: 13 weeks
measure: Controlled Oral Word Association Test
timeFrame: 13 Weeks
measure: Stroop Interference Test
timeFrame: 13 Weeks
measure: Symbol-Digit Modality Test
timeFrame: 13 Weeks
measure: Trail Making Test Part B
timeFrame: 13 Weeks
Secondary outcomes:
measure: Hopkins Verbal Learning Total Recall Test
timeFrame: 13 weeks
measure: Semantic Fluency Test
timeFrame: 13 Weeks
Other outcomes:
Locations:
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
Study officials:
affiliation: Loyola University
name: Mary A Byrn, Ph.D., R.N.
role: PRINCIPAL_INVESTIGATOR
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