Reversing Diabetic Peripheral Neuropathy Through Exercise

This project proposes a longitudinal design that uses multinuclear-MRI to evaluate the mechanistic effects of exercise on skeletal muscle function and peripheral nerve integrity in patients with diabetic peripheral neuropathy (DPN), and to determine whether exercise can reverse DPN symptoms. The investigators will prescribe a 10-week exercise program to 40 DPN patients. The investigators will acquire multinuclear-MRI data before and after the intervention that can provide mechanistic insight into the adaptations in lower leg muscle function and peripheral nerve integrity of patients with DPN, and their role in improving DPN symptoms following physical exercise intervention.

Study Overview

• Status: Completed
• Conditions: Diabetes; Peripheral Neuropathy
• Intervention / Treatment: Procedure: Exercise Program

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10016
      • New York University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 36 years to 66 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Be between the ages of 40 and 70
• Clinical diagnosis of Type 2 diabetes
• Clinical diagnosis of DPN
• Have a BMI less than 40 kg/m2 (due to magnet bore restrictions)
• Able to walk unassisted

Exclusion Criteria:

• Serious cardiac pathology or musculoskeletal problems that would limit exercise ability
• MNSI score < 1
• Current open wound or history of plantar ulcer for the last 3 months
• Partial foot amputations
• Inability to ambulate without assistive device
• Stroke or other central nervous system pathology
• Stage 2 hypertension (resting blood pressure >160 systolic or >100 diastolic)
• Contraindications to 3T whole body MRI scanners (e.g., pacemaker, cerebral aneurysm clip, cochlear implant, presence of shrapnel in strategic locations, metal in the eye, claustrophobia, or other problems).
• Subjects with alcoholism, chronic drug use, chronic gastrointestinal disease, or renal or hepatic impairment
• Pregnant women and children

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patients with Type 2 Diabetes and Clinical Symptoms of DPN; Patients will be individually prescribed to a 10-week exercise program with both aerobic and resistance components. Prior to beginning the intervention, patients will participate in a maximal graded exercise test (VO2R) using a cycle ergometer with a metabolic cart and integrated ECG.	Procedure: Exercise Program; The exercise program will combine moderate intensity aerobic exercise with lower-extremity specific resistance training. A moderate level of intensity will be calculated based on results from a maximal graded exercise test (VO2R) conducted prior to the intervention.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Body Mass Index (BMI)	The BMI calculation divides an adult's weight in kilograms by their height in meters squared.	Baseline
Change From Baseline in Body Mass Index (BMI)	The BMI calculation divides an adult's weight in kilograms by their height in meters squared.	Week 10
Glycosylated Hemoglobin (HbA1c)	The glycosylated hemoglobin test shows what a person's average blood glucose level was for the 2 to 3 months before the test. Measured via patient blood samples.	Baseline
Glycosylated Hemoglobin (HbA1c)	The glycosylated hemoglobin test shows what a person's average blood glucose level was for the 2 to 3 months before the test. Measured via patient blood samples.	Week 10
C-Reactive Protein Levels	Measured via patient blood samples.	Baseline
C-Reactive Protein Levels	Measured via patient blood samples.	Week 10
Michigan Neuropathy Screening Instrument (MNSI) Symptom Questionnaire	15-question assessment of symptoms. Responses of "yes" to items 1-3, 5-6, 8-9, 11-12, 14-15 are each counted as one point. A "no" response on items 7 and 13 counts as 1 point. Item 4 is a measure of impaired circulation and item 10 is a measure of general asthenia; neither are included in scoring. The total score ranges from 0-13; lower scores indicate less prevalent symptoms; a decrease in scores indicates symptoms decreased during the observational period.	Baseline
Michigan Neuropathy Screening Instrument (MNSI) Symptom Questionnaire	15-question assessment of symptoms. Responses of "yes" to items 1-3, 5-6, 8-9, 11-12, 14-15 are each counted as one point. A "no" response on items 7 and 13 counts as 1 point. Item 4 is a measure of impaired circulation and item 10 is a measure of general asthenia; neither are included in scoring. The total score ranges from 0-13; lower scores indicate less prevalent symptoms; a decrease in scores indicates symptoms decreased during the observational period.	Week 10
MNSI Physical Exam Score	Completed by physician. Assessment of abnormalities in the appearance of the feet, vibration sense, reflexes, and monofilament sensation. The total score ranges from 0-10; lower scores indicate greater physical health; a decrease in scores indicates physical health increased during the observational period.	Baseline
MNSI Physical Exam Score	Completed by physician. Assessment of abnormalities in the appearance of the feet, vibration sense, reflexes, and monofilament sensation. The total score ranges from 0-10; lower scores indicate greater physical health; a decrease in scores indicates physical health increased during the observational period.	Week 10
Calf Muscle Performance	Performance will be quantified as peak ankle plantarflexion torque at 60 degrees/sec.	Baseline
Calf Muscle Performance	Performance will be quantified as peak ankle plantarflexion torque at 60 degrees/sec.	Week 10
Physical Performance Test (PP) Score	9-item assessment of Physical Performance. The total score ranges from 0 to 36; higher scores indicate greater levels of physical performance.	Baseline
Physical Performance Test (PP) Score	9-item assessment of Physical Performance. The total score ranges from 0 to 36; higher scores indicate greater levels of physical performance.	Week 10
PCr Resynthesis Rate in the Gastrocnemius Muscle Groups	Measured using multinuclear-MRI following a 90-second plantar flexion exercise during which resistance is applied at approximately 40% of the individual's maximum voluntary contraction. The value reported in the data table represents the average flexion across both calf muscles.	Baseline
PCr Resynthesis Rate in the Gastrocnemius Muscle Groups	Measured using multinuclear-MRI following a 90-second plantar flexion exercise during which resistance is applied at approximately 40% of the individual's maximum voluntary contraction. The value reported in the data table represents the average flexion across both calf muscles.	Week 10
Intramuscular Adipose Tissue (IMAT) Levels in the Gastrocnemius Muscle Groups	Measured using IDEAL-MRI. IMAT levels are quantified as a percentage of total tissue in the gastrocnemius muscle groups of both calf muscles combined.	Baseline
Intramuscular Adipose Tissue (IMAT) Levels in the Gastrocnemius Muscle Groups	Measured using IDEAL-MRI. IMAT levels are quantified as a percentage of total tissue in the gastrocnemius muscle groups of both calf muscles combined.	Week 10
IMAT Levels in the Soleus Muscle Groups	Measured using IDEAL-MRI. IMAT levels are quantified as a percentage of total tissue in the soleus muscle groups of both calf muscles combined.	Baseline
IMAT Levels in the Soleus Muscle Groups	Measured using IDEAL-MRI. IMAT levels are quantified as a percentage of total tissue in the soleus muscle groups of both calf muscles combined.	Week 10
Fractional Anisotropy (FA) in the Tibial Nerve	FA is a scalar value between zero and one that describes the degree of anisotropy of a diffusion process. A value of zero means that diffusion is isotropic, i.e. it is unrestricted (or equally restricted) in all directions. A value of one means that diffusion occurs only along one axis and is fully restricted along all other directions. Measured using Diffusion Tensor Imaging (DTI).	Baseline
Fractional Anisotropy (FA) in the Tibial Nerve	FA is a scalar value between zero and one that describes the degree of anisotropy of a diffusion process. A value of zero means that diffusion is isotropic, i.e. it is unrestricted (or equally restricted) in all directions. A value of one means that diffusion occurs only along one axis and is fully restricted along all other directions. Measured using Diffusion Tensor Imaging (DTI).	Week 10
Apparent Diffusion Coefficient (ADC) in the Tibial Nerve	ADC is a measure of the magnitude of diffusion (of water molecules) within tissue. Measured using DTI.	Baseline
Apparent Diffusion Coefficient (ADC) in the Tibial Nerve	ADC is a measure of the magnitude of diffusion (of water molecules) within tissue. Measured using DTI.	Week 10

Collaborators and Investigators

• Sponsor: NYU Langone Health
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: Ryan Brown, PhD, NYU Langone Health

Study record dates

Study Major Dates

• Study Start (Actual): November 28, 2018
• Primary Completion (Actual): June 30, 2022
• Study Completion (Actual): June 30, 2022

Study Registration Dates

• First Submitted: September 25, 2018
• First Submitted That Met QC Criteria: September 25, 2018
• First Posted (Actual): September 27, 2018

Study Record Updates

• Last Update Posted (Actual): May 17, 2023
• Last Update Submitted That Met QC Criteria: April 24, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Exercise
• Additional Relevant MeSH Terms: Nervous System Diseases; Neuromuscular Diseases; Peripheral Nervous System Diseases
• Other Study ID Numbers: 18-00527

Drug and device information, study documents

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