ADAPT Study

Principal Investigator: Rob Singleton
Keywords: diabetic nerve pain , diabetes , peripheral neuropathy , exercise , dietary counseling Department: Neurology
IRB Number: 00072011 Co Investigator:  
Specialty: Physical Therapy, Audiology, Audiology, Neurology
Sub Specialties: Neurophysiology, Balance/Vestibular, Neuropathy
Recruitment Status: Recruiting

Contact Information

Angela Stonebraker
angela.stonebraker@hsc.utah.edu
8015852741

Brief Summary

Type 2 diabetes (T2D) affects >8% of Americans, half of whom develop diabetic peripheral neuropathy (DPN).  DPN is a major cause for disability due to sensory loss, pain, gait instability, falls, foot ulcers and amputations.  There are no effective disease altering therapies for DPN in T2D.  Even intensive glycemic control, which is of proven benefit in T1D, is only marginally effective in reducing DPN risk in T2D.

            Unfortunately, intensive exercise is of limited long-term efficacy due to poor compliance and the behavioral pattern of compensatory increase in caloric intact and sedentary behavior.  We hypothesize that an intervention integrating moderate supervised exercise with actigraphy based strategies to reduce sedentary behavior will result in sustainable metabolic improvement, and that this novel strategy will slow the rate of IENFD decline and improve neuropathy specific quality of life in patients with DPN due to T2D.

            We hypothesize the intervention will improve insulin sensitivity and reduce oxidative stress and inflammation, resulting in enhanced peripheral nerve regenerative capacity. The Activity for Diabetic Polyneuropathy – ADAPT Study will randomize 140 T2D patients with mild to moderate DPN to either generic annual counseling or an integrated program of moderate supervised exercise and actigraphy based anti-sedentariness counseling.  IENFD at the distal thigh and the Norfolk Quality of Life – Diabetic Neuropathy (NQOL-DN) will serve as primary endpoint measures.  The study will be judged positive if one endpoint is significantly positive and the other is not significantly negative.

            The primary goal is to determine if this novel approach to increasing home activity and reduced sedentary time is an effective therapy for DPN using change in IENFD and the NQOL-DN as co-primary endpoints.  A second objective is to better evaluate the clinical meaning of change in IENFD.  Skin biopsies will be used to explore the intervention’s impact on epidermal regeneration and inflammation.  Skin, serum and DNA will be banked for future mechanistic studies. As a third aim, a substudy will determine if the metabolic improvement anticipated with this unique intervention alters vestibular function, as measured by tests of balance.

Inclusion Criteria

 

1. T2D defined by ADA criteria.

2. Peripheral neuropathy based on the Toronto Diabetic Neuropathy Expert Group consensus criteria for “Confirmed diabetic sensorimotor peripheral neuropathy”.

3. Moderate DPN severity with a UENS of 2-18.

4. Age between 30 and 75. 

5. Under the care of an identified Primary Care Physician (PCP).

 

 

Exclusion Criteria

1. Any alternative cause for peripheral neuropathy.  The following tests must have been found normal within the last 12 months or will be performed pre-randomization:  vitamin B12, serum protein electrophoresis and immunofixation.  ANA and TSH may be obtained if clinically indicated and not available from clinical records.

2. Family history of a non-diabetic neuropathy in a first-degree relative.

3. Severe or longstanding neuropathy: UENS > 18 or history of foot ulceration or amputation.

4. Participants taking Coumadin or oral factor X or thrombin inhibitor therapy will be considered on an individual basis by the site investigator.

5. Severe edema, dermatologic or lower extremity condition that would increase risk of skin biopsy.

6. A serious medical condition that might shorten life span or prevent exercise.

7. Subjects with obesity or hypertension considered in a dangerous range (BMI> 45, systolic BP >170, or diastolic BP >110) and those who fail a medically supervised graded maximal stress test will be excluded from the study for safety reasons.

    8.  An inability to understand or cooperate with the procedures of the study

9.  Females who are pregnant at screening or actively plan to become pregnant during the study period, because of the marked changes in metabolism anticipated during pregnancy.

10.  If ,in the investigators assessment, that participation in the study would be limited by a person's weight, size, or other physical condition.