Effect of Exercise and Surgical Weight Loss on Polyneuropathy

NCT03617185 | Completed Results DMC

• 2 other identifiers: HUM001435411R01DK115687-01A1
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research study is to evaluate how exercise and surgical weight loss affect how likely an individual is to develop peripheral neuropathy and other neurologic complications.

Conditions

Polyneuropathies; Obesity; Bariatric Surgery Candidate

Keywords

Metabolic syndrome; Exercise

Outcome Measures

Primary Outcomes (1)

• Intraepidermal Nerve Fiber Density (IENFD) at the Proximal Thigh

  Intraepidermal Nerve Fiber Density (IENFD) as assessed by 3mm skin biopsies at the proximal thigh.

  Baseline, 3 months, 12 months and 24 months

Secondary Outcomes (34)

• Intraepidermal Nerve Fiber Density (IENFD) at Distal Leg.

  Baseline, 3 months, 12 months and 24 months

• Corneal Confocal Microscopy (CCM) - Fiber Density

  Baseline, 3 month, 12 months and 24 months

• Corneal Confocal Microscopy (CCM) - Branch Density

  Baseline, 3 month, 12 months and 24 months

• Corneal Confocal Microscopy (CCM) - Fiber Length

  Baseline, 3 month, 12 months and 24 months

• Corneal Confocal Microscopy (CCM) - Tortuosity Coefficient

  Baseline, 3 month, 12 months and 24 months

Study Arms (4)

Bariatric Surgery/HIIT

ACTIVE COMPARATOR

Patients who have undergone bariatric surgery will be randomized to this arm and will follow a high intensity interval training (HIIT) protocol for 24 months. Patients will complete 2 supervised HIIT sessions and 1 unsupervised HIIT session a week.

Other: High Intensity Interval Training (HIIT); Procedure: Bariatric surgery

Bariatric Surgery/Routine Exercise

ACTIVE COMPARATOR

Patients who have undergone bariatric surgery will be randomized to this arm and will follow a standard routine exercise regimen for 24 months.

Other: Routine Exercise; Procedure: Bariatric surgery

No Bariatric Surgery/HIIT

ACTIVE COMPARATOR

Patients who have not undergone bariatric surgery will be randomized to this arm and will follow a high intensity interval training (HIIT) protocol for 24 months. Patients will complete 2 supervised HIIT sessions and 1 unsupervised HIIT session a week.

Other: High Intensity Interval Training (HIIT)

No Bariatric Surgery/Routine Exercise

ACTIVE COMPARATOR

Patients who have not undergone bariatric surgery will be randomized to this arm and will follow a standard routine exercise regimen for 24 months.

Other: Routine Exercise

Interventions

High Intensity Interval Training (HIIT) OTHER

Patients will complete a HIIT training protocol of a total of 10 x 1 min intervals at 90% heart rate (HR) max. They will continue this training protocol, 3 sessions a week (2 supervised and 1 unsupervised), for 24 months.

Bariatric Surgery/HIIT; No Bariatric Surgery/HIIT

Routine Exercise OTHER

Patients will receive counseling regarding exercise as a routine part of their participation in the bariatric surgery clinic. Specifically, they are counseled to participate in 60 min of aerobic exercise daily in addition to 2-3 non-consecutive days of strength training workouts every wk. Patients are encouraged to contact the bariatric conditioning program, obtain a gym membership, purchase exercise equipment, join a walking group, and/or sign up for fitness classes (employer or city parks and recreation).

Bariatric Surgery/Routine Exercise; No Bariatric Surgery/Routine Exercise

Bariatric surgery PROCEDURE

Patients will undergo bariatric surgery as part of their routine care

Bariatric Surgery/HIIT; Bariatric Surgery/Routine Exercise

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Attending a bariatric surgery clinic
• BMI \> 35 with one comorbid condition present or BMI \> 40 without comorbid conditions present
• Willing and capable to sign the Institutional Review Board (IRB) approved consent form and cooperate with the medical procedures for the study duration
• Willing to accept random treatment assignment to HIIT or routine exercise counseling

You may not qualify if:

• History of distal symmetric polyneuropathy (DSP) from causes other than diabetes and/or the metabolic syndrome as determined through medical history, family history, history of medications, occupational history, history of exposure to toxins, physical and neurological examinations;
• Use of warfarin, heparin, or other anticoagulants, which would increase the risk of complications from skin biopsy
• Contraindication to HIIT participation including a failed exercise stress test
• Participation in an experimental medication trial within 3 months of starting the study
• Undergoing therapy for malignant disease other than basal-cell or squamous-cell skin cancer
• Medical or psychiatric reason for not being a surgical candidate
• Requiring a walking assist device;
• Currently smoking

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator
• University of Michigan: lead

Study Sites (1)

University Of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Related Publications (1)

• Reynolds EL, Koenig F, Watanabe M, Kwiatek A, Elafros MA, Stino A, Henderson D, Herrmann DN, Feldman EL, Callaghan BC. Comparison of intraepidermal nerve fiber density and confocal corneal microscopy for neuropathy. Ann Clin Transl Neurol. 2024 Dec;11(12):3115-3124. doi: 10.1002/acn3.52218. Epub 2024 Oct 12.

  PMID: 39394845 DERIVED

MeSH Terms

Conditions

Polyneuropathies; Obesity; Metabolic Syndrome; Motor Activity

Interventions

High-Intensity Interval Training; Bariatric Surgery

Condition Hierarchy (Ancestors)

Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Behavior

Intervention Hierarchy (Ancestors)

Physical Conditioning, Human; Exercise; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Bariatrics; Obesity Management; Therapeutics; Surgical Procedures, Operative

Results Point of Contact

• Title: Brian Callaghan, MD
• Organization: University of Michigan

Bcallagh@med.umich.edu

7349367183

Study Officials

• Brian C Callaghan, MD, MS

  University of Michigan, Department of Neurology

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The neuropathy outcomes assessors will be blinded to the exercise protocol that the patients are randomized to and the surgical status for the duration of the study.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Fovette E Dush Early Career Professor and Assistant Professor of Neurology

Model Details: Patients will be assigned to one of 4 arms, bariatric surgery/HIIT, bariatric surgery/routine exercise, no bariatric surgery/HIIT, no bariatric surgery/routine exercise.

Study Record Dates

• First Submitted: July 14, 2018
• First Posted: August 6, 2018
• Study Start: July 27, 2018
• Primary Completion: August 1, 2024
• Study Completion: August 1, 2024
• Last Updated: February 24, 2026
• Results First Posted: October 29, 2025

Record last verified: 2026-02

Locations

US (1)