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

NCT02416193 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: 206988206988031815
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

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.

Conditions

Diabetes; Executive Dysfunction

Keywords

Diabetes; Cognition; Functioning

Outcome Measures

Primary Outcomes (5)

• 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

• 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

• 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

• 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

• 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 Outcomes (2)

• Hopkins Verbal Learning Total Recall Test

  13 weeks

• Semantic Fluency Test

  13 Weeks

Study Arms (2)

High Dose

EXPERIMENTAL

50,000 IU cholecalciferol once weekly for three months

Drug: Cholecalciferol

Low Dose

ACTIVE COMPARATOR

5,000 IU cholecalciferol once weekly for three months

Drug: Cholecalciferol

Interventions

Cholecalciferol DRUG

Participants will take randomly assigned high dose cholecalciferol once weekly for three months

Also known as: Vitamin D3

High Dose

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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%

Sponsors & Collaborators

• Loyola University: lead
• University of Chicago: collaborator

Study Sites (1)

Loyola University Medical Center

Maywood, Illinois, 60153, United States

Location

Related Publications (40)

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MeSH Terms

Conditions

Diabetes Mellitus

Interventions

Cholecalciferol

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Cholestenes; Cholestanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Sterols; Vitamin D; Secosteroids; Membrane Lipids; Lipids

Limitations and Caveats

The trial experienced early termination leading to small numbers of subjects analyzed.

Results Point of Contact

• Title: Mary Byrn, R.N., Ph.D.
• Organization: Loyola University Chicago

mbyrn@luc.edu

(773) 508-8973

Study Officials

• Mary A Byrn, Ph.D., R.N.

  Loyola University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: April 6, 2015
• First Posted: April 14, 2015
• Study Start: September 23, 2015
• Primary Completion: July 12, 2018
• Study Completion: July 12, 2018
• Last Updated: October 23, 2020
• Results First Posted: October 23, 2020

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)