Effect of Exercise and Surgical Weight Loss on Polyneuropathy

Study Overview
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Brief Summary
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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.

Detailed Description
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The length of this study, including screening is approximately 24 months. Patients at Bariatric Surgery Clinics will be recruited for this study. Both patients that decide to undergo bariatric surgery, and those that do not undergo surgery will be enrolled. Patients will be randomized to either a high intensity interval training (HIIT) or standard exercise regimen after eligibility is confirmed and the baseline visit is complete. All patients will complete follow-up appointments at 3 month, 12 months and 24 months. Patients that are randomized to the HIIT program will compete 2 supervised and 1 unsupervised training sessions a week for 24 months.

Official Title
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The Effect of High Intensity Interval Training and Surgical Weight Loss on Distal Symmetric Polyneuropathy Outcomes

Conditions
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Obesity, Polyneuropathies, Bariatric Surgery Candidate

Intervention / Treatment
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* Other: High Intensity Interval Training (HIIT)
* Other: Routine Exercise
* Procedure: Bariatric surgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 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.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Bariatric Surgery/HIIT<br>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)<br>* 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.<br>Procedure: Bariatric surgery<br>* Patients will undergo bariatric surgery as part of their routine care<br>|
| Active Comparator: Bariatric Surgery/Routine Exercise<br>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<br>* 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).<br>Procedure: Bariatric surgery<br>* Patients will undergo bariatric surgery as part of their routine care<br>|
| Active Comparator: No Bariatric Surgery/HIIT<br>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)<br>* 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.<br>|
| Active Comparator: No Bariatric Surgery/Routine Exercise<br>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<br>* 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).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Intraepidermal Nerve Fiber Density (IENFD) at the proximal thigh | As assessed by 3mm skin biopsies.Linear mixed effects regression modeling will account for multiple time points of the same measure. | Baseline, 3 months, 12 months and 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Intraepidermal Nerve Fiber Density (IENFD) at distal leg. | As assessed by 3mm skin biopsies. Linear mixed effects regression modeling will account for multiple time points of the same measure. | Baseline, 3 months, 12 months and 24 months | 
| Corneal Confocal Microscopy (CCM) |  | Baseline, 3 month, 12 months and 24 months | 
| 24-2 Frequency Doubling Technology (FDT) |  | Baseline, 3 month, 12 months and 24 months | 
| Retinal Fundus Photography |  | Baseline, 3 month, 12 months and 24 months | 
| Nerve Conduction Study (NCS) | Sural, peroneal, and tibial nerves. | Baseline and 24 months | 
| Cardiac Autonomic Neuropathy Testing | Deep breathing-E:I ratio | Baseline and 24 months | 
| Cardiac Autonomic Neuropathy Testing | Postural change-30:15 ratio | Baseline and 24 months | 
| Cardiac Autonomic Neuropathy Testing | Valsalva- Valsalva ratio | Baseline and 24 months | 
| Incidence of polyneuropathy as defined by the Toronto definition of probable neuropathy | Toronto definition of probable neuropathy-2 out of 3 of abnormal sensory examination, reflexes, and symptoms. | 24 months | 
| Michigan Neuropathy Screening Instrument (MNSI) |  | Baseline, 3 month, 12 months and 24 months | 
| Utah Early Neuropathy Score | Scale 0-48, higher is more severe polyneuropathy | Baseline, 3 month, 12 months and 24 months | 
| Modified Toronto Neuropathy Score (mTNS) | Range 0-33, higher is more severe polyneuropathy | Baseline, 3 month, 12 months and 24 months | 
| Survey of Autonomic Symptoms (SAS) |  | Baseline, 3 month, 12 months and 24 months | 
| Diabetic Neuropathy Score (DNS) | Range 0-4, >/=1 indicates polyneuropathy | Baseline, 3 month, 12 months and 24 months | 
| Short Form McGill Pain Questionnaire |  | Baseline, 3 months, 12 months, 24 months | 
| Numerical Rating Scale for pain | Range 0-10, higher score indicates more pain | Baseline, 3 months, 12 months, 24 months | 
| Neuropathy Quality of Life (NeuroQOL) |  | Baseline, 3 months, 12 months, and 24 months | 
| Berg Balance Scale | Range 0-56, higher score indicates less likely to fall | Baseline, 3 months, 12 months, and 24 months | 
| 8 Foot Get Up and Go Test |  | Baseline, 3 months, 12 months, and 24 months | 
| Modified Falls Efficacy Scale | Range 0-140, higher score indicates less likely to fall | Baseline, 3 months, 12 months, and 24 months | 
| Neurothesiometer |  | Baseline, 3 months, 12 months, and 24 months | 
| NIH Toolbox Cognitive Battery |  | Baseline and at 24 months | 
| Rey Auditory Verbal Learning Test |  | Baseline and at 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metabolic syndrome, Exercise