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

September 30, 2020 updated by: Mary A Byrn, Loyola University
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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

56

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Illinois
      • Maywood, Illinois, United States, 60153
        • Loyola University Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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%

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: High Dose
50,000 IU cholecalciferol once weekly for three months
Drug: Cholecalciferol
Participants will take randomly assigned high dose cholecalciferol once weekly for three months
Other Names:
  • Vitamin D3
Drug: Cholecalciferol
Participants will take randomly assigned active comparator cholecalciferol once weekly for three months
Other Names:
  • Vitamin D3
Active Comparator: Low Dose
5,000 IU cholecalciferol once weekly for three months
Drug: Cholecalciferol
Participants will take randomly assigned high dose cholecalciferol once weekly for three months
Other Names:
  • Vitamin D3
Drug: Cholecalciferol
Participants will take randomly assigned active comparator cholecalciferol once weekly for three months
Other Names:
  • Vitamin D3

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Letter-Number Sequencing
Time Frame: 13 weeks
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
Controlled Oral Word Association Test
Time Frame: 13 Weeks
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
Stroop Interference Test
Time Frame: 13 Weeks
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
Symbol-Digit Modality Test
Time Frame: 13 Weeks
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
Trail Making Test Part B
Time Frame: 13 Weeks
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Hopkins Verbal Learning Total Recall Test
Time Frame: 13 weeks
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
Semantic Fluency Test
Time Frame: 13 Weeks
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Loyola University

Collaborators

University of Chicago

Investigators

  • Principal Investigator: Mary A Byrn, Ph.D., R.N., Loyola University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 23, 2015

Primary Completion (Actual)

July 12, 2018

Study Completion (Actual)

July 12, 2018

Study Registration Dates

First Submitted

April 6, 2015

First Submitted That Met QC Criteria

April 9, 2015

First Posted (Estimate)

April 14, 2015

Study Record Updates

Last Update Posted (Actual)

October 23, 2020

Last Update Submitted That Met QC Criteria

September 30, 2020

Last Verified

September 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 206988
  • 206988031815 (Other Identifier: Loyola University Chicago)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

IPD Plan Description

There is no plan to share individual participant data with other researchers

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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