Using Polar Unite Fitness Watch to Improve Cognition for T2DM Patients

Feasibility Testing a Randomized Controlled Trial of an mHealth-enhanced Exercise Program to Improve Cognition for T2DM Patients

Type 2 diabetes mellitus (T2DM) impairs the brain, leading to cognitive dysfunction, which carries substantial lifetime consequences. This highlights an urgent need to find effective therapeutic strategies to improve cognitive function among those with T2DM. Aerobic exercise enhances cognitive function among healthy subjects through increased release of BDNF. BDNF supports survival of existing neurons and promotes growth of new neurons and synapses. Emerging evidence suggests that reduced BDNF levels may exacerbate cognitive dysfunction associated with T2DM. Compared to drug delivery of BDNF, aerobic exercise is a low-cost, safe, and easily accessible path to increasing endogenous BDNF levels. One critical genetic variant that affects BDNF secretion and cognition is the BDNF Val66Met variant, which is a common missense polymorphism that results in a valine (Val) to methionine (Met) substitution at codon 66 located in exon IX of the BDNF gene. The Met allele alters intracellular processing, trafficking, packaging of pro-BDNF, and consequently interferes with the activity-dependent secretion of mature BDNF among Met carriers. In addition, previous research reported an influence of the Val66Met variant on the methylation level of the surrounding region. Carrying a G nucleotide (i.e., Val allele) will have an additional CpG site, and Val/Val homozygotes demonstrated a significant increase in methylation levels of four nearby CpG sites compared to Val/Met heterozygotes and Met/Met homozygotes. Because high BDNF gene methylation is associated with reduced BDNF mRNA levels, this may result in lower BDNF levels among Val/Val carriers. However, the transcription of promoter IV can be initiated by exercise, suggesting that epigenetic modulation of BDNF gene expression may be achieved by exercise. It is plausible that exercise may partly reverse transcriptional repression through dynamic DNA demethylation, but the interaction between DNA demethylation and Val homozygosity may be different from that in Met/Met and in Val/Met carriers, which could explain interpersonal differences in cognitive outcomes among these carriers following exercise training. So far, the evidence on the interplay of the Val66Met polymorphism, DNA methylation, and exercise on cognition among individuals with T2DM is still lacking. A total of 42 participants with T2DM will be randomized 2:1 to receive aerobic exercise intervention (n=28) or attention control (n=14) for 3 months. Both groups will receive weekly phone calls during the intervention and standard printed education materials regarding diabetes self-management. In addition to these interventions, the aerobic exercise group (i.e., experimental group) will also perform home-based walking exercise, while the attention control group will perform home-based stretching exercise. Trained students will monitor the exercise sessions for both groups at the Connected Health Platform (hereafter referred to as "platform"). Blood samples will be collected at baseline and three months. Outcomes of interest include post-intervention changes in plasma BDNF levels, BDNF DNA methylation executive function, memory, and processing speed. The study will evaluate the feasibility of the home-based exercise intervention. The study will also evaluate preliminary effectiveness of the supervised exercise program on of the exercise program on BDNF DNA demethylation. An exploratory aim is to explore the association of DNA demethylation with plasma BDNF levels and cognition.

Study Overview

• Status: Unknown
• Conditions: Diabetes Mellitus, Type 2, Cognitive Dysfunction, Epigenetics, Exercise
• Intervention / Treatment: Behavioral: Aerobic exercise program; Behavioral: Stretching exercise

• Study Type: Interventional
• Enrollment (Anticipated): 42
• Phase: Not Applicable

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Participants eligible for this study will be physically inactive adults with no major chronic physical or mental disorders but classified as having low physical activity levels determined by the International Physical Activity Questionnaire. Participants must have a documented medical diagnosis of T2DM and must be receiving diabetes care at the time of enrollment. Participants must be English-speaking and are able to give informed consent.

Exclusion Criteria:

• Exclusion criteria include uncontrolled hypertension with resting blood pressure of 160/90 mmHg or higher, having symptoms of coronary ischemia such as chest pain and severe shortness of breath during activities of daily living, loss of consciousness/fainting for any reason, or having any other medical or physical conditions that may interfere with exercise participation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Aerobic exercise group; Aerobic exercise will be measured with a Polar United fitness watch. Heart rate during exercise will be measured using a Polar United fitness watch, which has been validated for monitoring moderate and high intensity physical activity.	Behavioral: Aerobic exercise program; A randomized controlled trial will be used to test the feasibility of a home-based exercise program to improve BDNF DNA demethylation among individuals with T2DM. A total of 42 participants will be randomized 2:1 to receive aerobic exercise intervention (n=28) or attention control (n=14) for 3 months. This ratio is used to offset an anticipated attrition imbalance across groups.
Placebo Comparator: Attention control group; The time-equivalent, stretching movements will serve as the placebo exercise condition in this proposed study. Previous research has shown that stretching could reduce attrition and patient dissatisfaction and better ensure allocation concealment. Following baseline measures, a student will demonstrate the use of a Polar United fitness watch and stretching movements via zoom from week 3 to week 5. Starting on week 3, participants will perform the prescribed stretching exercise 3 times a week, maintaining heart rate below 40% of heart rate reserve during exercise.	Behavioral: Stretching exercise; stretching exercise

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
BDNF DNA demethylation in percentage	Three months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma BDNF levels in ng		Three months
Executive function	Executive function will be measured by the Dimensional Change Card Sort Test. Test-retest reliability of the test is 0.88. Convergent validity and discriminant validity is -0.51 and 0.14, respectively.	Three months
Episodic memory	Episodic memory will be measured by the Picture Sequence Memory Test. Test-retest reliability of the test is 0.77. Convergent validity and discriminant validity is 0.69 and -0.08, respectively.	Three months
Working memory	Working memory will be measured by the List Sorting Working Memory Test. Test-retest reliability of the test is 0.77. Convergent validity and discriminant validity are 0.58 and 0.30, respectively.	Three months
Processing speed	Processing speed will be measured by the Pattern Comparison Processing Speed Test. The test takes about 3 minutes to compete. Test-retest reliability of the test is 0.72. Convergent validity and discriminant validity is 0.49 and 0.12, respectively.	Three months

Collaborators and Investigators

• Sponsor: University of Arkansas, Fayetteville

Study record dates

Study Major Dates

• Study Start (Anticipated): October 27, 2020
• Primary Completion (Anticipated): May 15, 2021
• Study Completion (Anticipated): July 15, 2021

Study Registration Dates

• First Submitted: October 21, 2020
• First Submitted That Met QC Criteria: October 26, 2020
• First Posted (Actual): October 27, 2020

Study Record Updates

• Last Update Posted (Actual): October 27, 2020
• Last Update Submitted That Met QC Criteria: October 26, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Glucose Metabolism Disorders; Metabolic Diseases; Neurocognitive Disorders; Endocrine System Diseases; Diabetes Mellitus; Cognition Disorders; Diabetes Mellitus, Type 2; Cognitive Dysfunction
• Other Study ID Numbers: 2009284124

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No