Can Vitamin D3 Improve Cognitive Function in Individuals With Type 2 Diabetes? (THINK-D)

Diabetes Clinical Trial

— THINK-D  

Official title:

Can Vitamin D3 Improve Cognitive Function in Individuals With Type 2 Diabetes? (THINK-D)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02416193
• Other study ID #: 206988
• Secondary ID: 206988031815
• Status: Terminated
• Phase: Phase 2
• Start date: September 23, 2015
• Est. completion date: July 12, 2018

Study information

• Verified date: September 2020
• Source: Loyola University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 56
• Est. completion date: July 12, 2018
• Est. primary completion date: July 12, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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%

Related Conditions & MeSH terms

• Diabetes
• Diabetes Mellitus
• Executive Dysfunction

Intervention

Drug:
• Cholecalciferol
Participants will take randomly assigned high dose cholecalciferol once weekly for three months
• Cholecalciferol
Participants will take randomly assigned active comparator cholecalciferol once weekly for three months

Locations

Country	Name	City	State
United States	Loyola University Medical Center	Maywood	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
Loyola University	University of Chicago

Country where clinical trial is conducted

United States, 

References & Publications (40)

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* Note: There are 40 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Letter-Number Sequencing	The the Letter-Number Sequencing Test (from the Wechsler Adult Intelligence Scale-III assessment) is an assessment of working memory. Scores on the assessment are standardized as scaled scores with a mean of 10 and standard deviation of 3 (µ = 10, SD = 3) using age adjusted normative data provided by Pearson assessments (https://www.pearsonassessments.com/). A scaled score indicates the number of standard deviations away from the mean. A scaled score of 10 is equal to the mean. Scaled scores below 10 indicate performance is lower than average, and scaled scores higher than 10 indicate performance is higher than average. Higher scaled scores indicate better performance.	13 weeks
Primary	Controlled Oral Word Association Test	The Controlled Oral Word Association Test is a measure of verbal fluency. Scores are standardized as z-scores (µ = 0, SD = 1) using age adjusted normative data provided by Tombaugh and Kozak (1996). A z-score indicates the number of standard deviations away from the mean. A z-score of 0 is equal to the mean. Negative z-scores indicate performance is lower than average, and positive z-scores indicate performance is higher than average. Positive z-scores indicate better performance.	13 Weeks
Primary	Stroop Interference Test	The Stroop Interference Test is a measure of executive functioning. Scores are standardized as z-scores (µ = 0, SD = 1) using age adjusted normative data provided by PAR Incorporated (https://www.parinc.com/). A z-score indicates the number of standard deviations away from the mean. A z-score of 0 is equal to the mean. Negative z-scores indicate performance is lower than average, and positive z-scores indicate performance is higher than average. Positive z-scores indicate better performance.	13 Weeks
Primary	Symbol-Digit Modality Test	The Symbol-Digit Modality Test is a measure of executive functioning. Scores are standardized as z-scores (µ = 0, SD = 1) using age adjusted normative data provided by WPS Publishers (https://www.wpspublish.com/). A z-score indicates the number of standard deviations away from the mean. A z-score of 0 is equal to the mean. Negative z-scores indicate performance is lower than average, and positive z-scores indicate performance is higher than average. Positive z-scores indicate better performance.	13 Weeks
Primary	Trail Making Test Part B	The Trail Making Test Part B is a measure of executive functioning. Scores are standardized as z-scores (µ = 0, SD = 1) using age adjusted normative data provided by WPS Publishers (https://www.wpspublish.com/). A z-score indicates the number of standard deviations away from the mean. A z-score of 0 is equal to the mean. Negative z-scores indicate performance is lower than average, and positive z-scores indicate performance is higher than average. Positive z-scores indicate better performance.	13 Weeks
Secondary	Hopkins Verbal Learning Total Recall Test	The Hopkins Verbal Learning Total Recall Test is an assessment of memory. Scores are standardized as T-scores (µ = 50, SD = 10) using age adjusted normative data provided by PAR Incorporated (https://www.parinc.com/). A T-score indicates the number of standard deviations away from the mean. A T-score of 50 is equal to the mean. T-scores below 50 indicate performance is lower than average, and T-scores above 50 indicate performance is higher than average. Higher T-scores indicate better performance.	13 weeks
Secondary	Semantic Fluency Test	The Semantic Fluency Test is a measure of verbal fluency. Scores are standardized as z-scores (µ = 0, SD = 1) using age adjusted normative data provided by Tombaugh and Kozak (1996). A z-score indicates the number of standard deviations away from the mean. A z-score of 0 is equal to the mean. Negative z-scores indicate performance is lower than average, and positive z-scores indicate performance is higher than average. Positive z-scores indicate better performance.	13 Weeks