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Completed

NCT Number: NCT00955201

Exercise-facilitated Neurorehabilitation in Diabetic Neuropathy

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.

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Key information

Conditions

Diabetic Neuropathy Diabetes Complications Diabetes Mellitus Diabetic Neuropathies Endocrine System Diseases Glucose Metabolism Disorders Metabolic Diseases Nervous System Diseases Neuromuscular Diseases Nutritional and Metabolic Diseases Peripheral Nervous System Diseases

Age range

45 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Edward Hines Jr. VA Hospital, Hines, IL

Hines, Illinois, 60141-5000, United States

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Exercise

Behavioral

Structured aerobic exercise (treadmill).

Primary outcomes

  1. Sural Nerve Amplitude

    Time frame: Baseline, 12, and 24 weeks

    Maximal responses were obtained using percutaneous electrical stimuli. Sensory nerve action potentials were recorded from sural (antidromic), median (antidromic to second digit), and ulnar nerves (antidromic to fifth digit).To minimize inter-examiner variability and maximize neurophysiologic test/retest reliability, the same experienced neurologist conducted all nerve conduction studies on days separate from all other testing activities. A dedicated TECA Synergy electromyograph system was used for all nerve conduction studies. The patients dominant side was chosen. In patients with definable differences between the two sides, the side with the most prominent clinical findings was chosen. In all cases, the same limb was used for all three (baseline, 12-weeks, 24-weeks) conduction studies.

  2. Sural Nerve Latency

    Time frame: Baseline, 12 wks, 24 wks

    Maximal responses were obtained using percutaneous electrical stimuli. Sensory nerve action potentials were recorded from sural (antidromic), median (antidromic to second digit), and ulnar nerves (antidromic to fifth digit).To minimize inter-examiner variability and maximize neurophysiologic test/retest reliability, the same experienced neurologist conducted all nerve conduction studies on days separate from all other testing activities. A dedicated TECA Synergy electromyograph system was used for all nerve conduction studies. The patients dominant side was chosen. In patients with definable differences between the two sides, the side with the most prominent clinical findings was chosen. In all cases, the same limb was used for all three (baseline, 12-weeks, 24-weeks) conduction studies.

  3. Sural Nerve Conduction Velocity

    Time frame: Baseline, 12 wks, 24 wks

    Maximal responses were obtained using percutaneous electrical stimuli. Sensory nerve action potentials were recorded from sural (antidromic), median (antidromic to second digit), and ulnar nerves (antidromic to fifth digit).To minimize inter-examiner variability and maximize neurophysiologic test/retest reliability, the same experienced neurologist conducted all nerve conduction studies on days separate from all other testing activities. A dedicated TECA Synergy electromyograph system was used for all nerve conduction studies. The patients dominant side was chosen. In patients with definable differences between the two sides, the side with the most prominent clinical findings was chosen. In all cases, the same limb was used for all three (baseline, 12-weeks, 24-weeks) conduction studies.

  4. Tibial Nerve Amplitude

    Time frame: Baseline, 12 weeks, 24 weeks

    Maximal responses were obtained using percutaneous electrical stimuli. Distal motor nerve evoked compound muscle action potential (CMAP) potentials were recorded from tibial and peroneal nerves.To minimize inter-examiner variability and maximize neurophysiologic test/retest reliability, the same experienced neurologist conducted all nerve conduction studies on days separate from all other testing activities. A dedicated TECA Synergy electromyograph system was used for all nerve conduction studies. The patients dominant side was chosen. In patients with definable differences between the two sides, the side with the most prominent clinical findings was chosen. In all cases, the same limb was used for all three (baseline, 12-weeks, 24-weeks) conduction studies.

  5. Tibial Nerve Latency

    Time frame: Baseline, 12 weeks, 24 weeks

    Maximal responses were obtained using percutaneous electrical stimuli. Distal motor nerve evoked compound muscle action potential (CMAP) potentials were recorded from tibial and peroneal nerves.To minimize inter-examiner variability and maximize neurophysiologic test/retest reliability, the same experienced neurologist conducted all nerve conduction studies on days separate from all other testing activities. A dedicated TECA Synergy electromyograph system was used for all nerve conduction studies. The patients dominant side was chosen. In patients with definable differences between the two sides, the side with the most prominent clinical findings was chosen. In all cases, the same limb was used for all three (baseline, 12-weeks, 24-weeks) conduction studies.

  6. Tibial Nerve Conduction Velocity

    Time frame: Baseline, 12 weeks, 24 weeks

    Maximal responses were obtained using percutaneous electrical stimuli. Distal motor nerve evoked compound muscle action potential (CMAP) potentials were recorded from tibial and peroneal nerves.To minimize inter-examiner variability and maximize neurophysiologic test/retest reliability, the same experienced neurologist conducted all nerve conduction studies on days separate from all other testing activities. A dedicated TECA Synergy electromyograph system was used for all nerve conduction studies. The patients dominant side was chosen. In patients with definable differences between the two sides, the side with the most prominent clinical findings was chosen. In all cases, the same limb was used for all three (baseline, 12-weeks, 24-weeks) conduction studies.

  7. Sensory Median Nerve Amplitude

    Time frame: Baseline, 12, and 24 weeks

    Maximal responses were obtained using percutaneous electrical stimuli. Sensory nerve action potentials were recorded from sural (antidromic), median (antidromic to second digit), and ulnar nerves (antidromic to fifth digit).To minimize inter-examiner variability and maximize neurophysiologic test/retest reliability, the same experienced neurologist conducted all nerve conduction studies on days separate from all other testing activities. A dedicated TECA Synergy electromyograph system was used for all nerve conduction studies. The patients dominant side was chosen. In patients with definable differences between the two sides, the side with the most prominent clinical findings was chosen. In all cases, the same limb was used for all three (baseline, 12-weeks, 24-weeks) conduction studies.

  8. Sensory Median Nerve Latency

    Time frame: Baseline, 12wks, 24 wks

    Maximal responses were obtained using percutaneous electrical stimuli. Sensory nerve action potentials were recorded from sural (antidromic), median (antidromic to second digit), and ulnar nerves (antidromic to fifth digit).To minimize inter-examiner variability and maximize neurophysiologic test/retest reliability, the same experienced neurologist conducted all nerve conduction studies on days separate from all other testing activities. A dedicated TECA Synergy electromyograph system was used for all nerve conduction studies. The patients dominant side was chosen. In patients with definable differences between the two sides, the side with the most prominent clinical findings was chosen. In all cases, the same limb was used for all three (baseline, 12-weeks, 24-weeks) conduction studies.

  9. Sensory Median Nerve Conduction Velocity

    Time frame: Baseline, 12 wks, 24 wks

    Maximal responses were obtained using percutaneous electrical stimuli. Sensory nerve action potentials were recorded from sural (antidromic), median (antidromic to second digit), and ulnar nerves (antidromic to fifth digit).To minimize inter-examiner variability and maximize neurophysiologic test/retest reliability, the same experienced neurologist conducted all nerve conduction studies on days separate from all other testing activities. A dedicated TECA Synergy electromyograph system was used for all nerve conduction studies. The patients dominant side was chosen. In patients with definable differences between the two sides, the side with the most prominent clinical findings was chosen. In all cases, the same limb was used for all three (baseline, 12-weeks, 24-weeks) conduction studies.

  10. Sensory Ulnar Nerve Amplitude

    Time frame: Baseline, 12 wks, 24 wks

    Maximal responses were obtained using percutaneous electrical stimuli. Sensory nerve action potentials were recorded from sural (antidromic), median (antidromic to second digit), and ulnar nerves (antidromic to fifth digit).To minimize inter-examiner variability and maximize neurophysiologic test/retest reliability, the same experienced neurologist conducted all nerve conduction studies on days separate from all other testing activities. A dedicated TECA Synergy electromyograph system was used for all nerve conduction studies. The patients dominant side was chosen. In patients with definable differences between the two sides, the side with the most prominent clinical findings was chosen. In all cases, the same limb was used for all three (baseline, 12-weeks, 24-weeks) conduction studies.

  11. Sensory Ulnar Nerve Latency

    Time frame: Baseline, 12 wks, 24 wks

    Maximal responses were obtained using percutaneous electrical stimuli. Sensory nerve action potentials were recorded from sural (antidromic), median (antidromic to second digit), and ulnar nerves (antidromic to fifth digit).To minimize inter-examiner variability and maximize neurophysiologic test/retest reliability, the same experienced neurologist conducted all nerve conduction studies on days separate from all other testing activities. A dedicated TECA Synergy electromyograph system was used for all nerve conduction studies. The patients dominant side was chosen. In patients with definable differences between the two sides, the side with the most prominent clinical findings was chosen. In all cases, the same limb was used for all three (baseline, 12-weeks, 24-weeks) conduction studies.

  12. Sensory Ulnar Nerve Conduction Velocity

    Time frame: Baseline, 12 wks, 24 wks

    Maximal responses were obtained using percutaneous electrical stimuli. Sensory nerve action potentials were recorded from sural (antidromic), median (antidromic to second digit), and ulnar nerves (antidromic to fifth digit).To minimize inter-examiner variability and maximize neurophysiologic test/retest reliability, the same experienced neurologist conducted all nerve conduction studies on days separate from all other testing activities. A dedicated TECA Synergy electromyograph system was used for all nerve conduction studies. The patients dominant side was chosen. In patients with definable differences between the two sides, the side with the most prominent clinical findings was chosen. In all cases, the same limb was used for all three (baseline, 12-weeks, 24-weeks) conduction studies.

  13. Peroneal Nerve Amplitude

    Time frame: Baseline, 12 wks, 24 wks

    Maximal responses were obtained using percutaneous electrical stimuli. Distal motor nerve evoked compound muscle action potential (CMAP) potentials were recorded from tibial and peroneal nerves.To minimize inter-examiner variability and maximize neurophysiologic test/retest reliability, the same experienced neurologist conducted all nerve conduction studies on days separate from all other testing activities. A dedicated TECA Synergy electromyograph system was used for all nerve conduction studies. The patients dominant side was chosen. In patients with definable differences between the two sides, the side with the most prominent clinical findings was chosen. In all cases, the same limb was used for all three (baseline, 12-weeks, 24-weeks) conduction studies.

  14. Peroneal Nerve Latency

    Time frame: Baseline, 12 wks, 24 wks

    Maximal responses were obtained using percutaneous electrical stimuli. Distal motor nerve evoked compound muscle action potential (CMAP) potentials were recorded from tibial and peroneal nerves.To minimize inter-examiner variability and maximize neurophysiologic test/retest reliability, the same experienced neurologist conducted all nerve conduction studies on days separate from all other testing activities. A dedicated TECA Synergy electromyograph system was used for all nerve conduction studies. The patients dominant side was chosen. In patients with definable differences between the two sides, the side with the most prominent clinical findings was chosen. In all cases, the same limb was used for all three (baseline, 12-weeks, 24-weeks) conduction studies.

  15. Peroneal Nerve Conduction Velocity

    Time frame: Baseline, 12 wks, 24 wks

    Maximal responses were obtained using percutaneous electrical stimuli. Distal motor nerve evoked compound muscle action potential (CMAP) potentials were recorded from tibial and peroneal nerves.To minimize inter-examiner variability and maximize neurophysiologic test/retest reliability, the same experienced neurologist conducted all nerve conduction studies on days separate from all other testing activities. A dedicated TECA Synergy electromyograph system was used for all nerve conduction studies. The patients dominant side was chosen. In patients with definable differences between the two sides, the side with the most prominent clinical findings was chosen. In all cases, the same limb was used for all three (baseline, 12-weeks, 24-weeks) conduction studies.

Secondary outcomes

  1. Symptom-Limited TMT Blood Glucose Response

    Time frame: Initial entry into study, 12 and 24 weeks

    Changes in blood glucose in response to modified Bruce Protocol treadmill test (TMT)

  2. Short Form-36V: Physical Component Score

    Time frame: Initial entry into study, 12 and 24 weeks

    The short form-36Veterans (SF-36V) health survey questionnaire was used to measure health-related quality of life. This survey is comprised of eight subscales and two overall component scores, all of which have demonstrated high levels of internal consistency and discriminate validity when administered to groups of medically stable individuals. Patient aggregate responses for the eight distinct summary subscales and two component scores were compiled as a percentage of total points possible using the RAND 36-item health survey table. Data shown are expressed as a percentage of total possible score ranging from 0%-100% with 100% considered relatively good health and 0% considered poor health. Physical Component scores reflect perceived changes in physical health relative to the previous year.

  3. Voluntary Duration of Symptom-Limited TMT

    Time frame: baseline, 12-wks, 24-wks

    Total time subjects voluntarily exercised while undergoing a modified Bruce Protocol treadmill test (TMT)

  4. Symptom-Limited TMT Maximum Heart Rate

    Time frame: baseline, 12-wks, 24-wks

    Peak heart rate achieved while undergoing a modified Bruce Protocol treadmill test (TMT)

  5. Symptom-Limited TMT Maximum Systolic Blood Pressure

    Time frame: Baseline, 12-wk, 24-wk

    Peak systolic BP achieved while undergoing a modified Bruce Protocol treadmill test (TMT)

  6. Symptom-Limited TMT Maximum Minute Ventilation (VE)

    Time frame: Baseline, 12-wks, 24-wks

    Peak volume of air exchanged per minute achieved while undergoing a modified Bruce Protocol treadmill test (TMT)

  7. Symptom-Limited TMT Maximum Oxygen Uptake (VO2)

    Time frame: Baseline, 12-wks, 24-wks

    Peak Oxygen uptake achieved while undergoing a modified Bruce Protocol treadmill test (TMT)

  8. Maximum Respiratory Exchange Ratio (RER) During TMT

    Time frame: Baseline, 12-wks, 24-wks

    Peak RER achieved while undergoing a modified Bruce Protocol treadmill test (TMT). This is a mathematical ratio of maximally achieved (peak) VCO2 divided by maximally achieved (peak) VO2.

  9. Symptom-Limited TMT Maximum Carbon Dioxide Expelled (VCO2)

    Time frame: Baseline, 12-wks, 24-wks

    Peak Carbon Dioxide expelled achieved while undergoing a modified Bruce Protocol treadmill test (TMT)

  10. Symptom-Limited TMT Maximum METS Achieved (MET)

    Time frame: Baseline, 12-wks, 24-wks

    Peak metabolic rate equivalents (METS) achieved while undergoing a modified Bruce Protocol treadmill test (TMT). One MET is defined as the metabolic rate observed at rest, quantified as resting oxygen consumption of 250 ml/min (Male) or 200 ml /min (female). A value of 5 METS would represent a metabolic rate that is 5x that at rest and is considered an indicator of how hard a given individual is exercising. Data shown are expressed as a ratio at peak of exercise of oxygen consumed relative to normalized values for men or women at rest.

  11. Short Form-36V: Mental Component Score

    Time frame: initial entry into study, and at 12-wks and 24-wks

    The short form-36Veterans (SF-36V) health survey questionnaire was used to measure health-related quality of life. This survey is comprised of eight subscales and two overall component scores, all of which have demonstrated high levels of internal consistency and discriminate validity when administered to groups of medically stable individuals. Patient aggregate responses for the eight distinct summary subscales and two component scores were compiled as a percentage of total points possible using the RAND 36-item health survey table. Data shown are expressed as a percentage of total possible score ranging from 0%-100% with 100% considered relatively good health and 0% considered poor health. Mental Component scores reflect perceived changes in emotional health relative to the previous year.

Other outcomes

  1. Height

    Time frame: baseline

    Height of subjects upon entry into study

  2. Weight

    Time frame: Baseline, 12-wks, 24-wks

    Weight of subjects at baseline, 12-weeks, and 24-weeks

  3. Body Mass Index (BMI)

    Time frame: Baseline, 12-wk, 24-wk

    BMI is calculated as a ratio of subject body mass (kg) divided by the square of subject height (m).

  4. Duration of Diabetes Mellitus

    Time frame: Baseline

    Duration, in years, since first diagnosed with Diabetes Mellitus upon entry into study

  5. HbA1C Laboratory Values

    Time frame: Baseline, 12-wk, 24-wk

    Laboratory values of subject HbA1C levels at Baseline, 12-wk, 24-wk

  6. Triglyceride Laboratory Values

    Time frame: Baseline

    Laboratory triglyceride values at baseline entry into study

  7. Cholesterol Laboratory Values

    Time frame: Baseline

    Laboratory total cholesterol, HDL-cholesterol, and LDL-cholesterol levels at baseline entry into study

  8. Creatinine Laboratory Values

    Time frame: Baseline

    Laboratory creatinine values at baseline entry into study

  9. Blood Urea Nitrogen (BUN) Laboratory Values

    Time frame: Baseline

    Laboratory Blood Urea Nitrogen levels at baseline entry into study

  10. Aspartate Aminotransferase Laboratory Values

    Time frame: Baseline

    Laboratory values for Aspartate Aminotransferase (AST) at baseline entry into study

  11. Thyroid Stimulating Hormone Laboratory Values

    Time frame: Baseline

    Laboratory values for Thyroid Stimulating Hormone (TSH) at baseline entry into study

  12. Age

    Time frame: at baseline

    Age of participants at entry into study.

Sponsors and collaborators

Lead sponsor

VA Office of Research and Development

Fed

Registry information

Important dates

Study start
2010
Primary completion
2014
Study completion
2014
First posted
Aug 10, 2009
Registry last updated
Oct 2, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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