Clinical trial NCT00955201: Exercise-facilitated Neurorehabilitation in Diabetic Neuropathy
Official title: Exercise-Facilitated NeuroRehabilitation in Diabetic Neuropathy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Diabetic Neuropathy
Keywords: diabetes mellitus
diabetic neuropathies
Aerobic Exercise
Exercise Therapy
electromyography
United States Veterans
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
First posted: 2009-08-10
Enrollment: 45
Sex: ALL
Minimum age (years): 45
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: This study will determine the type and combination of exercise needed to rehabilitate the neuro-compromised diabetic Veteran. Guided exercise protocols may prove to be practical therapeutic options for the prophylactic management of diabetic subjects with neuropathy.

Detailed description: Purpose: A single-site, randomized, blinded, prospective clinical trial is proposed to determine the significance of a combined isokinetic strength and aerobic exercise training program on the rehabilitation of peripheral nerve function in Type 2 diabetic veterans and non-veterans with neuropathy. Background and Significance: Obesity is a major factor in the increasing rates of diabetes and its related complications. Diabetes affects greater than 7% of the population. Veterans are at even greater risk, with approximately 16% currently receiving treatment at Department of Veterans Affairs Medical Centers for diabetes. More than half of affected veterans experience debilitating complications of diabetes, including peripheral neuropathy (PN). Exercise training, in combination with pharmacologic intervention, is now recognized as a cornerstone of management for diabetes. Therapeutic interventions currently available for the treatment of PN in diabetic patients are limited, however, to pain management and stringent glycemic control. Exercise is reported to significantly decrease peripheral nerve microvascular complications common among chronic diabetics. Our preliminary findings demonstrate that exercise intervention improves peripheral nerve function in the diabetic veteran with PN. Intervention strategies, such as proposed in this application, offer a unique and novel therapeutic option for the rehabilitation of the neuro-compromised Type 2 diabetic veterans and non-veterans. Methods \& Research Plan: One-hundred subjects will be recruited for this 24-week study. Subjects each will be randomly assigned to aerobic, isokinetic strength training, combined aerobic and strength training, or non-exercise (control) intervention groups. Isokinetic strength training (Biodex System 3), aerobic exercise training (treadmill), or the combination of strength and aerobic training will be administered 3x per week for the initial 12 weeks. Control subjects will receive 12 clinical visits over the course of the initial 12 weeks. The effects of exercise training type, compared with control subjects, on recovery of peripheral nerve function will be rigorously determined from baseline, 12- and 24-week testing using electrodiagnostic primary outcome measures, Quantitative Sensory Testing, and a battery of validated qualitative and quantitative secondary outcome measures that include an incremental symptom-limited treadmill test, peak torque, Total Neuropathy Score, visual analogue pain scale, and quality of life SF-36V Health Survey. Sustainability of effect will be determined at 24-weeks.The individual effects of exercise training type, compared with control subjects, on tissue oxygenation will be determined from baseline, 12- and 24-week testing by non-invasive quantitated infrared spectroscopy using an InSpectraTM Tissue Spectrometer. Expected Outcomes: This study will objectively and critically determine the type and combination of exercise needed to rehabilitate the neuro-compromised diabetic Veteran. Guided exercise protocols may prove to be practical therapeutic options for the prophylactic management of diabetic subjects with neuropathy.

Eligibility criteria: Inclusion Criteria:

* Clinical diagnosis of type 2 diabetes mellitus
* stable blood glucose control
* clinical findings consistent with length-dependent sensorimotor polyneuropathy, stage N2a

Exclusion Criteria:

* foot ulceration
* unstable heart disease
* co-morbid conditions limiting exercise
* disorders of the central nervous system causing weakness or sensory loss
* received treatment with medications known to have neuropathy as a prominent side effect including vincristine, vinblastine, cis-platin, and paclitaxel
* medical conditions that may be associated with neuropathies such as alcoholism, liver disease, kidney disease, toxic exposure, vitamin deficiency, autoimmune disorders, cancer, or hypothyroidism

Primary outcomes:
measure: Sural Nerve Amplitude
timeFrame: Baseline, 12, and 24 weeks
measure: Sural Nerve Latency
timeFrame: Baseline, 12 wks, 24 wks
measure: Sural Nerve Conduction Velocity
timeFrame: Baseline, 12 wks, 24 wks
measure: Tibial Nerve Amplitude
timeFrame: Baseline, 12 weeks, 24 weeks
measure: Tibial Nerve Latency
timeFrame: Baseline, 12 weeks, 24 weeks
measure: Tibial Nerve Conduction Velocity
timeFrame: Baseline, 12 weeks, 24 weeks
measure: Sensory Median Nerve Amplitude
timeFrame: Baseline, 12, and 24 weeks
measure: Sensory Median Nerve Latency
timeFrame: Baseline, 12wks, 24 wks
measure: Sensory Median Nerve Conduction Velocity
timeFrame: Baseline, 12 wks, 24 wks
measure: Sensory Ulnar Nerve Amplitude
timeFrame: Baseline, 12 wks, 24 wks
measure: Sensory Ulnar Nerve Latency
timeFrame: Baseline, 12 wks, 24 wks
measure: Sensory Ulnar Nerve Conduction Velocity
timeFrame: Baseline, 12 wks, 24 wks
measure: Peroneal Nerve Amplitude
timeFrame: Baseline, 12 wks, 24 wks
measure: Peroneal Nerve Latency
timeFrame: Baseline, 12 wks, 24 wks
measure: Peroneal Nerve Conduction Velocity
timeFrame: Baseline, 12 wks, 24 wks
Secondary outcomes:
measure: Symptom-Limited TMT Blood Glucose Response
timeFrame: Initial entry into study, 12 and 24 weeks
measure: Short Form-36V: Physical Component Score
timeFrame: Initial entry into study, 12 and 24 weeks
measure: Voluntary Duration of Symptom-Limited TMT
timeFrame: baseline, 12-wks, 24-wks
measure: Symptom-Limited TMT Maximum Heart Rate
timeFrame: baseline, 12-wks, 24-wks
measure: Symptom-Limited TMT Maximum Systolic Blood Pressure
timeFrame: Baseline, 12-wk, 24-wk
measure: Symptom-Limited TMT Maximum Minute Ventilation (VE)
timeFrame: Baseline, 12-wks, 24-wks
measure: Symptom-Limited TMT Maximum Oxygen Uptake (VO2)
timeFrame: Baseline, 12-wks, 24-wks
measure: Maximum Respiratory Exchange Ratio (RER) During TMT
timeFrame: Baseline, 12-wks, 24-wks
measure: Symptom-Limited TMT Maximum Carbon Dioxide Expelled (VCO2)
timeFrame: Baseline, 12-wks, 24-wks
measure: Symptom-Limited TMT Maximum METS Achieved (MET)
timeFrame: Baseline, 12-wks, 24-wks
measure: Short Form-36V: Mental Component Score
timeFrame: initial entry into study, and at 12-wks and 24-wks
Other outcomes:
measure: Height
timeFrame: baseline
measure: Weight
timeFrame: Baseline, 12-wks, 24-wks
measure: Body Mass Index (BMI)
timeFrame: Baseline, 12-wk, 24-wk
measure: Duration of Diabetes Mellitus
timeFrame: Baseline
measure: HbA1C Laboratory Values
timeFrame: Baseline, 12-wk, 24-wk
measure: Triglyceride Laboratory Values
timeFrame: Baseline
measure: Cholesterol Laboratory Values
timeFrame: Baseline
measure: Creatinine Laboratory Values
timeFrame: Baseline
measure: Blood Urea Nitrogen (BUN) Laboratory Values
timeFrame: Baseline
measure: Aspartate Aminotransferase Laboratory Values
timeFrame: Baseline
measure: Thyroid Stimulating Hormone Laboratory Values
timeFrame: Baseline
measure: Age
timeFrame: at baseline
Locations:
city: Hines
country: United States
facility: Edward Hines Jr. VA Hospital, Hines, IL
state: Illinois
Study officials:
affiliation: Edward Hines Jr. VA Hospital, Hines, IL
name: Evan Stubbs
role: PRINCIPAL_INVESTIGATOR
References:
citation: Stubbs EB Jr, Fisher MA, Miller CM, Jelinek C, Butler J, McBurney C, Collins EG. Randomized Controlled Trial of Physical Exercise in Diabetic Veterans With Length-Dependent Distal Symmetric Polyneuropathy. Front Neurosci. 2019 Feb 11;13:51. doi: 10.3389/fnins.2019.00051. eCollection 2019.