Activity for Diabetic Polyneuropathy (ADAPT): Study Design and Protocol for a 2-Site Randomized Controlled Trial

Abstract

Background: Half of all patients with diabetes develop diabetic peripheral neuropathy (DPN), a complication leading to reduced mobility and quality of life. Although there are no proven pharmacologic approaches to reduce DPN risk or slow its progression, evidence suggests that physical activity may improve symptoms and enhance peripheral nerve regeneration.

Objective: The aim of the study will be to determine the impact of an intense lifestyle intervention on neuropathy progression and quality of life in individuals with DPN.

Design: The study will be a randomized controlled trial.

Setting: The study will be conducted at 2 academic medical centers.

Participants: The participants will be 140 individuals with type 2 diabetes and mild to moderate DPN.

Intervention: The intervention group will receive 18 months of supervised exercise training, actigraphy-based counseling to reduce sedentary behavior, and individualized dietary counseling. Control group participants will receive diet and activity counseling at baseline and at 9 months.

Measurements: The primary outcomes are neuropathy progression as measured by intraepidermal nerve fiber density in a distal thigh skin biopsy and the Norfolk Quality of Life-Diabetic Neuropathy score. Secondary outcomes include pain, gait, balance, and mobility measures.

Limitations: Due to the combined intervention approach, this protocol will not be able to determine which intervention components influence outcomes. There also may be difficulty with participant attrition during the 18-month study intervention.

Conclusions: The Activity for Diabetic Polyneuropathy (ADAPT) protocol resulted from a collaboration between physical therapists and neurologist researchers that includes as primary outcomes both a quality-of-life measure (NQOL-DN) and a physiologic biomarker (IENFD). It has the potential to demonstrate that an intensive lifestyle intervention may be a sustainable, clinically effective approach for people with DPN that improves patient outcomes and can have an immediate impact on patient care and future clinical trials.

Trial registration: ClinicalTrials.gov NCT02341261.

© 2017 American Physical Therapy Association

Figures

Figure.

Conceptual model for the mediation analysis. This analysis will explore the extent to which the intervention affects quality of life directly via a general health effect (1) or via intermediary variables such as pain, sensory loss, fall risk, and mobility. The treatment effects can either occur independent of intraepidermal nerve fiber density (IENFD) effects (2) or be “mediated” by IENFD (3). Lastly, it is possible that a portion of the treatment benefit could be mediated purely by IENFD without influence of the other intermediate variables (4). DPN=diabetic peripheral neuropathy.

Appendix.

Interview Guide

Appendix.

Interview Guide