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NCT03617185

Effect of Exercise and Surgical Weight Loss on Polyneuropathy

Completed NA Results posted Last updated 24 February 2026
What this trial tests

NA trial testing High Intensity Interval Training (HIIT) in Polyneuropathies in 140 participants. Completed in 1 August 2024.

Timeline
27 July 2018
Primary endpoint
1 August 2024
1 August 2024

Quick facts

Lead sponsorUniversity of Michigan
PhaseNA
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingsingle
Primary purposetreatment
Enrollment140
Start date27 July 2018
Primary completion1 August 2024
Estimated completion1 August 2024
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

University of Michigan

Who can join

40 and older, any sex, with Polyneuropathies or Obesity. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Intraepidermal Nerve Fiber Density (IENFD) at the Proximal Thigh Primary · Baseline, 3 months, 12 months and 24 months

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

Baseline
GroupValue95% CI
Bariatric Surgery/HIIT11.9± 3.9
Bariatric Surgery/Routine Exercise12.7± 4.4
No Bariatric Surgery/HIIT9.8± 4.9
No Bariatric Surgery/Routine Exercise11± 4.6
3 Months
GroupValue95% CI
Bariatric Surgery/HIIT12.6± 3.9
Bariatric Surgery/Routine Exercise14.3± 5
No Bariatric Surgery/HIIT9.9± 4.2
No Bariatric Surgery/Routine Exercise10.6± 6
12 Months
GroupValue95% CI
Bariatric Surgery/HIIT11.5± 6.1
Bariatric Surgery/Routine Exercise14.2± 6.2
No Bariatric Surgery/HIIT9.2± 4.2
No Bariatric Surgery/Routine Exercise8.5± 4.4
24 Months
GroupValue95% CI
Bariatric Surgery/HIIT11.9± 6.0
Bariatric Surgery/Routine Exercise13.5± 6.2
No Bariatric Surgery/HIIT10.3± 4.3
No Bariatric Surgery/Routine Exercise9.3± 3.8
Intraepidermal Nerve Fiber Density (IENFD) at Distal Leg. Secondary · Baseline, 3 months, 12 months and 24 months

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

Baseline
GroupValue95% CI
Bariatric Surgery/HIIT6.3± 4
Bariatric Surgery/Routine Exercise6.8± 4.3
No Bariatric Surgery/HIIT7.3± 4.1
No Bariatric Surgery/Routine Exercise5.7± 3.8
3 Months
GroupValue95% CI
Bariatric Surgery/HIIT7.3± 4.1
Bariatric Surgery/Routine Exercise6.2± 4.1
No Bariatric Surgery/HIIT6.3± 3.6
No Bariatric Surgery/Routine Exercise5.5± 3.8
12 Months
GroupValue95% CI
Bariatric Surgery/HIIT7.7± 5.2
Bariatric Surgery/Routine Exercise8.7± 5.4
No Bariatric Surgery/HIIT6.4± 3.6
No Bariatric Surgery/Routine Exercise6.4± 5.5
24 Months
GroupValue95% CI
Bariatric Surgery/HIIT6.9± 4.5
Bariatric Surgery/Routine Exercise7.4± 4.4
No Bariatric Surgery/HIIT6.4± 3.8
No Bariatric Surgery/Routine Exercise5.8± 4.1
Corneal Confocal Microscopy (CCM) - Fiber Density Secondary · Baseline, 3 month, 12 months and 24 months

Non-invasive imaging technique of the corneal nerves to quantify nerve density and morphology. Corneal Nerve Fiber Density are quantified by fibers/mm2, a higher number represents a higher density of fibers. Lower numbers indicate worse neuropathy.

Baseline-Corneal Nerve Fiber Density (fibers/mm2)
GroupValue95% CI
Bariatric Surgery/HIIT22.1± 6.8
Bariatric Surgery/Routine Exercise19.5± 5.7
No Bariatric Surgery/HIIT19.5± 6.2
No Bariatric Surgery/Routine Exercise22.4± 5.4
3 Months-Corneal Nerve Fiber Density (fibers/mm2)
GroupValue95% CI
Bariatric Surgery/HIIT20± 6.5
Bariatric Surgery/Routine Exercise19.9± 4.9
No Bariatric Surgery/HIIT19.3± 6.5
No Bariatric Surgery/Routine Exercise19.8± 6.3
12 Months-Corneal Nerve Fiber Density (fibers/mm2)
GroupValue95% CI
Bariatric Surgery/HIIT19.8± 9.4
Bariatric Surgery/Routine Exercise20.7± 5.2
No Bariatric Surgery/HIIT17.2± 6.3
No Bariatric Surgery/Routine Exercise18.8± 6.8
24 Months-Corneal Nerve Fiber Density (fibers/mm2)
GroupValue95% CI
Bariatric Surgery/HIIT20.5± 5.1
Bariatric Surgery/Routine Exercise20.2± 3.9
No Bariatric Surgery/HIIT19± 5.5
No Bariatric Surgery/Routine Exercise18.8± 5.7
Corneal Confocal Microscopy (CCM) - Branch Density Secondary · Baseline, 3 month, 12 months and 24 months

Non-invasive imaging technique of the corneal nerves to quantify nerve density and morphology. Corneal Nerve Branch Density are quantified by branches/mm2, a higher number represents a higher density of branches. Lower numbers indicate worse neuropathy.

Baseline-Corneal Nerve Branch Density (branches/mm2)
GroupValue95% CI
Bariatric Surgery/HIIT56.4± 30.7
Bariatric Surgery/Routine Exercise57.1± 24.6
No Bariatric Surgery/HIIT53.6± 31.9
No Bariatric Surgery/Routine Exercise54.7± 25.3
3 Months-Corneal Nerve Branch Density (branches/mm2)
GroupValue95% CI
Bariatric Surgery/HIIT62.2± 32
Bariatric Surgery/Routine Exercise72.6± 34
No Bariatric Surgery/HIIT62± 31.3
No Bariatric Surgery/Routine Exercise63.9± 37.2
12 Months-Corneal Nerve Branch Density (branches/mm2)
GroupValue95% CI
Bariatric Surgery/HIIT126.6± 68.6
Bariatric Surgery/Routine Exercise137.4± 55.
No Bariatric Surgery/HIIT101.2± 57.9
No Bariatric Surgery/Routine Exercise116.8± 79
24 Months-Corneal Nerve Branch Density (branches/mm2)
GroupValue95% CI
Bariatric Surgery/HIIT124.7± 54.3
Bariatric Surgery/Routine Exercise129.8± 39.7
No Bariatric Surgery/HIIT116.6± 49.1
No Bariatric Surgery/Routine Exercise127.1± 55.9
Corneal Confocal Microscopy (CCM) - Fiber Length Secondary · Baseline, 3 month, 12 months and 24 months

Non-invasive imaging technique of the corneal nerves to quantify nerve density and morphology. Corneal Nerve Fiber Length are quantified by mm/mm2, a higher number represents a higher total length of fibers. Lower numbers indicate worse neuropathy .

Baseline-Corneal Nerve Fiber Length (mm/mm2)
GroupValue95% CI
Bariatric Surgery/HIIT18.6± 6.1
Bariatric Surgery/Routine Exercise18.9± 5.3
No Bariatric Surgery/HIIT17.9± 6.1
No Bariatric Surgery/Routine Exercise19.3± 4.9
3 Months-Corneal Nerve Fiber Length (mm/mm2)
GroupValue95% CI
Bariatric Surgery/HIIT19± 5.9
Bariatric Surgery/Routine Exercise20.6± 5.3
No Bariatric Surgery/HIIT19.3± 5.5
No Bariatric Surgery/Routine Exercise19.3± 6.1
12 Months-Corneal Nerve Fiber Length (mm/mm2)
GroupValue95% CI
Bariatric Surgery/HIIT25.7± 7.5
Bariatric Surgery/Routine Exercise28± 6.7
No Bariatric Surgery/HIIT23± 8.1
No Bariatric Surgery/Routine Exercise24.7± 8.7
24 Months-Corneal Nerve Fiber Length (mm/mm2)
GroupValue95% CI
Bariatric Surgery/HIIT25.2± 6.8
Bariatric Surgery/Routine Exercise25.3± 4.8
No Bariatric Surgery/HIIT24± 6.9
No Bariatric Surgery/Routine Exercise25.2± 7.4
Corneal Confocal Microscopy (CCM) - Tortuosity Coefficient Secondary · Baseline, 3 month, 12 months and 24 months

Non-invasive imaging technique of the corneal nerves to quantify nerve density and morphology. Tortuosity Coefficient represents the total tortuosity (twisting/bending of nerves). As a coefficient the value is unitless, a higher value represents greater tortuosity. Lower numbers indicate worse neuropathy.

Baseline-Corneal Tortuosity (coefficient value)
GroupValue95% CI
Bariatric Surgery/HIIT19.4± 5.6
Bariatric Surgery/Routine Exercise19± 6.3
No Bariatric Surgery/HIIT18.6± 6.7
No Bariatric Surgery/Routine Exercise19.2± 4.9
3 Months-Corneal Tortuosity (coefficient value)
GroupValue95% CI
Bariatric Surgery/HIIT17.8± 4.3
Bariatric Surgery/Routine Exercise19.9± 5.6
No Bariatric Surgery/HIIT17.7± 4.6
No Bariatric Surgery/Routine Exercise18.5± 4.9
12 Months-Corneal Tortuosity (coefficient value)
GroupValue95% CI
Bariatric Surgery/HIIT20.8± 7.2
Bariatric Surgery/Routine Exercise20.6± 5.6
No Bariatric Surgery/HIIT20.1± 7.3
No Bariatric Surgery/Routine Exercise21.4± 5.8
24 Months-Corneal Tortuosity (coefficient value)
GroupValue95% CI
Bariatric Surgery/HIIT20± 10.1
Bariatric Surgery/Routine Exercise22± 7.8
No Bariatric Surgery/HIIT21± 4.9
No Bariatric Surgery/Routine Exercise20.1± 5.6
24-2 Frequency Doubling Technology (FDT) - Mean Deviation Secondary · Baseline, 3 month, 12 months and 24 months

24-2 FDT was used to evaluate retinopathy using visual field deficits. Mean Deviation is presented below. Mean deviation is the average difference from normal expected value in the patients' particular age group. Lower values indicate more visual deficit. Higher values indicate fewer visual deficit.

Baseline-Mean Deviation
GroupValue95% CI
Bariatric Surgery/HIIT-1.6± 4.2
Bariatric Surgery/Routine Exercise-1.6± 2.7
No Bariatric Surgery/HIIT-2± 4.1
No Bariatric Surgery/Routine Exercise-2.5± 4
3 Months-Mean Deviation
GroupValue95% CI
Bariatric Surgery/HIIT-1± 4.1
Bariatric Surgery/Routine Exercise-1.5± 2.7
No Bariatric Surgery/HIIT-1.7± 4
No Bariatric Surgery/Routine Exercise-2.8± 4.6
12 Months-Mean Deviation
GroupValue95% CI
Bariatric Surgery/HIIT-0.9± 3.2
Bariatric Surgery/Routine Exercise-1.3± 3.1
No Bariatric Surgery/HIIT-2.4± 3.8
No Bariatric Surgery/Routine Exercise-1.5± 4.3
24 Months-Mean Deviation
GroupValue95% CI
Bariatric Surgery/HIIT-1.1± 3.8
Bariatric Surgery/Routine Exercise-0.7± 2.7
No Bariatric Surgery/HIIT-2.3± 3.4
No Bariatric Surgery/Routine Exercise-2.1± 4.8
24-2 Frequency Doubling Technology (FDT) - Foveal Sensitivity dB Secondary · Baseline, 3 month, 12 months and 24 months

24-2 FDT was used to evaluate retinopathy using visual field deficits. Foveal sensitivity is presented below. Foveal sensitivity is the measurement of the fovea's light detection ability. Lower values suggest visual field deficits.

Baseline-Foveal Sensitivity
GroupValue95% CI
Bariatric Surgery/HIIT27.7± 4.5
Bariatric Surgery/Routine Exercise28.3± 3.5
No Bariatric Surgery/HIIT26.9± 4.9
No Bariatric Surgery/Routine Exercise25.4± 5.9
3 Months--Foveal Sensitivity
GroupValue95% CI
Bariatric Surgery/HIIT28.3± 5.3
Bariatric Surgery/Routine Exercise28.3± 4.5
No Bariatric Surgery/HIIT27.1± 4.1
No Bariatric Surgery/Routine Exercise26.4± 4.6
12 Months--Foveal Sensitivity
GroupValue95% CI
Bariatric Surgery/HIIT28.1± 4
Bariatric Surgery/Routine Exercise28.9± 3.6
No Bariatric Surgery/HIIT25.9± 5.5
No Bariatric Surgery/Routine Exercise28.3± 4.6
24 Months--Foveal Sensitivity
GroupValue95% CI
Bariatric Surgery/HIIT27± 5.3
Bariatric Surgery/Routine Exercise28.2± 4.5
No Bariatric Surgery/HIIT26.7± 5
No Bariatric Surgery/Routine Exercise26.5± 6.6
24-2 Frequency Doubling Technology (FDT) - Pattern SD Secondary · Baseline, 3 month, 12 months and 24 months

24-2 FDT was used to evaluate retinopathy using visual field deficits. Pattern SD (PSD) is presented below. PSD provides information about localized loss. A higher PSD indicates a non-uniform sensitivity loss and visual field deficit.

Baseline-Patter SD
GroupValue95% CI
Bariatric Surgery/HIIT3.4± 1.1
Bariatric Surgery/Routine Exercise3.1± 1.1
No Bariatric Surgery/HIIT3.3± 1.1
No Bariatric Surgery/Routine Exercise3.7± 1.3
3 Months-Patter SD
GroupValue95% CI
Bariatric Surgery/HIIT3.1± 1.1
Bariatric Surgery/Routine Exercise3.2± 1.3
No Bariatric Surgery/HIIT3.3± 1
No Bariatric Surgery/Routine Exercise3.9± 1.7
12 Months-Patter SD
GroupValue95% CI
Bariatric Surgery/HIIT3.2± 1.1
Bariatric Surgery/Routine Exercise3.3± 1.7
No Bariatric Surgery/HIIT3.5± 1.1
No Bariatric Surgery/Routine Exercise3.6± 1.6
24 Months-Patter SD
GroupValue95% CI
Bariatric Surgery/HIIT3.2± 0.8
Bariatric Surgery/Routine Exercise3.1± 0.7
No Bariatric Surgery/HIIT3.5± 1.1
No Bariatric Surgery/Routine Exercise3.9± 1.7
Retinal Fundus Photography Secondary · Baseline, 3 month, 12 months and 24 months

As assessed by fundus photographs, participants were identified as either having retinopathy or not having retinopathy. Data is shown as number of people with retinopathy at a particular study visit.

Baseline
GroupValue95% CI
Bariatric Surgery/HIIT0
Bariatric Surgery/Routine Exercise1
No Bariatric Surgery/HIIT1
No Bariatric Surgery/Routine Exercise1
3 Months
GroupValue95% CI
Bariatric Surgery/HIIT0
Bariatric Surgery/Routine Exercise0
No Bariatric Surgery/HIIT0
No Bariatric Surgery/Routine Exercise0
12 Months
GroupValue95% CI
Bariatric Surgery/HIIT0
Bariatric Surgery/Routine Exercise0
No Bariatric Surgery/HIIT0
No Bariatric Surgery/Routine Exercise0
24 Months
GroupValue95% CI
Bariatric Surgery/HIIT0
Bariatric Surgery/Routine Exercise0
No Bariatric Surgery/HIIT0
No Bariatric Surgery/Routine Exercise0
Nerve Conduction Study (NCS) - Latency Secondary · Baseline and 24 months

Latency measures the time in millisecond between stimulation and the recording electrode. Was performed on sural, peroneal, and tibial nerves. No response and abnormal values indicate neuropathy. * Peroneal: 0 - No response, \>6.5 - Abnormal * Sural: 0 - No response, \>4.5 - Abnormal * Tibial: 0 - No response, \>6.1 - Abnormal

Baseline-Peroneal distal motor latency (ms)
GroupValue95% CI
Bariatric Surgery/HIIT4.6± 0.8
Bariatric Surgery/Routine Exercise4.4± 0.6
No Bariatric Surgery/HIIT4.4± 0.7
No Bariatric Surgery/Routine Exercise4.5± 1
Baseline-Sural peak latency (ms)
GroupValue95% CI
Bariatric Surgery/HIIT3.8± 0.5
Bariatric Surgery/Routine Exercise3.7± 0.4
No Bariatric Surgery/HIIT3.6± 0.3
No Bariatric Surgery/Routine Exercise3.9± 0.4
Baseline-Tibial distal motor latency (ms)
GroupValue95% CI
Bariatric Surgery/HIIT4.8± 0.6
Bariatric Surgery/Routine Exercise4.9± 0.8
No Bariatric Surgery/HIIT4.5± 0.6
No Bariatric Surgery/Routine Exercise4.7± 0.7
24 Months-Peroneal distal motor latency (ms)
GroupValue95% CI
Bariatric Surgery/HIIT4.3± 0.5
Bariatric Surgery/Routine Exercise4.4± 0.7
No Bariatric Surgery/HIIT4.2± 0.7
No Bariatric Surgery/Routine Exercise4.2± 0.7
24 Months-Sural peak latency (ms)
GroupValue95% CI
Bariatric Surgery/HIIT3.5± 0.4
Bariatric Surgery/Routine Exercise3.5± 0.4
No Bariatric Surgery/HIIT3.6± 0.6
No Bariatric Surgery/Routine Exercise3.4± 0.5
24 Months-Tibial distal motor latency (ms)
GroupValue95% CI
Bariatric Surgery/HIIT4.3± 0.7
Bariatric Surgery/Routine Exercise4.4± 0.8
No Bariatric Surgery/HIIT4.3± 0.9
No Bariatric Surgery/Routine Exercise4.6± 1.1
Nerve Conduction Study (NCS) - Motor Amplitude Secondary · Baseline and 24 months

Amplitude measures the height of electrical signal (waveform) in millivolts produced by the stimulated motor nerve. Was performed on peroneal, and tibial nerves. No response and abnormal values indicate neuropathy. * Peroneal: 0 - No response, \< 1.1 - Abnormal * Tibial: 0 - No response, \<1.1 - Abnormal

Baseline-Peroneal amplitude (mV)
GroupValue95% CI
Bariatric Surgery/HIIT5.21± 2.39
Bariatric Surgery/Routine Exercise5.95± 3.05
No Bariatric Surgery/HIIT5.18± 2.56
No Bariatric Surgery/Routine Exercise6.25± 4.13
Baseline-Tibial amplitude (mV)
GroupValue95% CI
Bariatric Surgery/HIIT9.4± 3.59
Bariatric Surgery/Routine Exercise9.16± 4.55
No Bariatric Surgery/HIIT8.06± 4.4
No Bariatric Surgery/Routine Exercise7.59± 4.66
24 Months-Peroneal amplitude (mV)
GroupValue95% CI
Bariatric Surgery/HIIT4.9± 2.11
Bariatric Surgery/Routine Exercise6.23± 2.93
No Bariatric Surgery/HIIT4.93± 2.02
No Bariatric Surgery/Routine Exercise5.11± 4.04
24 Months-Tibial amplitude (mV)
GroupValue95% CI
Bariatric Surgery/HIIT9.65± 4.98
Bariatric Surgery/Routine Exercise9.28± 4.75
No Bariatric Surgery/HIIT8.54± 4.02
No Bariatric Surgery/Routine Exercise8.04± 4.22

Adverse events — posted to ClinicalTrials.gov

Time frame: 2 years. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Bariatric Surgery/HIIT
Serious: 0/35 (0%)
Deaths: 0/35
No Bariatric Surgery/HIIT
Serious: 0/35 (0%)
Deaths: 0/35
Bariatric Surgery/Routine Exercise
Serious: 0/35 (0%)
Deaths: 0/35
No Bariatric Surgery/Routine Exercise
Serious: 0/35 (0%)
Deaths: 0/35
Other adverse events (2 terms — click to expand)

ReactionSystemBariatric Surgery/HIITNo Bariatric Surgery/HIITBariatric Surgery/Routine …No Bariatric Surgery/Routi…
Infection at Skin Biopsy SiteInfections and infestations
Injury During ExerciseInjury, poisoning and procedural complications

Data from ClinicalTrials.gov NCT03617185 adverse events section.

Sponsor's own description

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.

Publications & conference data

7 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Diabetic neuropathy: what does the future hold?
    Callaghan BC, Gallagher G, Fridman V, Feldman EL. · · 2020 · cited 92× · PMID 31974731 · DOI 10.1007/s00125-020-05085-9
  2. Evolving concepts on the role of dyslipidemia, bioenergetics, and inflammation in the pathogenesis and treatment of diabetic peripheral neuropathy.
    Stino AM, Rumora AE, Kim B, Feldman EL. · · 2020 · cited 52× · PMID 32412144 · DOI 10.1111/jns.12387
  3. The emerging role of dyslipidemia in diabetic microvascular complications.
    Savelieff MG, Callaghan BC, Feldman EL. · · 2020 · cited 45× · PMID 32073426 · DOI 10.1097/med.0000000000000533
  4. Obesity-Associated Neuropathy: Recent Preclinical Studies and Proposed Mechanisms.
    Bonomo R, Kramer S, Aubert VM. · · 2022 · cited 20× · PMID 35152780 · DOI 10.1089/ars.2021.0278
  5. Recent updates in the treatment of diabetic polyneuropathy.
    Fan Q, Gordon Smith A. · · 2022 · cited 8× · PMID 36311537 · DOI 10.12703/r/11-30
  6. Comparison of intraepidermal nerve fiber density and confocal corneal microscopy for neuropathy.
    Reynolds EL, Koenig F, Watanabe M, Kwiatek A, et al · · 2024 · cited 5× · PMID 39394845 · DOI 10.1002/acn3.52218
  7. Comparing In-Person to Tele-Exercise High-Intensity Interval Training in Adults With Class II/III Obesity.
    Chionis L, Watanabe M, Reynolds EL, Kerrigan D, et al · · 2026 · PMID 42221408 · DOI 10.1016/j.aed.2025.12.021

Verify or expand the search:

Other trials of High Intensity Interval Training (HIIT)

Trials testing the same drug.

Other recruiting trials for Polyneuropathies

Currently open trials in the same condition.

Other University of Michigan trials

Trials by the same sponsor.

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Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03617185.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing