Improving Autonomic Function and Balance in Diabetic Neuropathy

Diabetes Clinical Trial

— IMABIN  

Official title:

Improving Autonomic Function and Balance in Diabetic Neuropathy

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01864460
• Other study ID #: E1030-R
• Status: Active, not recruiting
• Phase: N/A
• Start date: November 14, 2013
• Est. completion date: November 30, 2026

Study information

• Verified date: August 2023
• Source: VA Office of Research and Development
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Type 2 diabetes (DM2) affects nearly 20 million people in the United States while impaired glucose regulation (IGR), which includes impaired glucose tolerance (IGT), impaired fasting glucose (IFG), and early diabetes affects a considerably larger but unknown population group. At the current time there is no effective therapy to completely prevent, or reverse neuropathy associated with IGR and this represents a considerable challenge in rehabilitation. There is a particularly strong incentive to prevent IGT and related complications from advancing to DM2. IGR is a growing problem among all older adults and its strong association with many functional limitations, particularly mobility limitations, is not always recognized, even though diabetes-related disability occurs in up to 2/3 of older adults with diabetes and is associated with dependency, poor quality of life, and increased acute and long-term care utilization.

Autonomic dysfunction is a significant problem in subjects with IGT. The Preliminary Data shows that over 90% of subjects with IGT have an abnormal score on questionnaires about autonomic symptoms such as lightheadedness, dry mouth or dry eyes, pale or blue feet, feet that are colder than the rest of the body, decreased sweating in the feet or increased sweating in the hands, nausea or bloating after eating, persistent diarrhea or constipation, or leaking of urine. In addition, patients with IGR have impaired balance control. These factors can increase the risk of falls in affected subjects. A non-randomized and non-controlled study showed that a diet and exercise intervention in patients with diabetes led to an overall improvement in autonomic function. Furthermore, it was shown that standing balance can be improved with a balance intervention program.

However, there are no published studies that assess the effect of an intense physical activity intervention on autonomic function in IGR related neuropathy. This study will test an aerobic exercise and balance intervention in participants with IGR. The investigators will examine if an individually tailored, carefully monitored, Diet, Physical Activity, and Balance Enhancement Program (DPAEP) can improve autonomic function and balance control when compared to patients who receive standard care. Improving balance control and autonomic function can decrease the risk of falls and have a significant effect on the health of participants.

The research is also significant because it will test subjects either before they become diabetic, or at an early stage in their diabetes, thus enhancing the chance of reversing the autonomic neuropathy or balance impairment. Furthermore, the study is designed to test whether improvement in autonomic function and balance is associated with improvement in clinical outcomes, quality of life, and the metabolic state of participants. Thus, the proposed interventions are likely to have a real life impact on participants and their health.

Description:

Study on hold due to COVID-19

In this proposed study, investigators will determine if an intense, individually tailored, carefully monitored, Diet, Physical Activity and Balance Enhancement Program (DPAEP) can improve autonomic function and balance and other measures of autonomic and balance control. In contrast, the primary and secondary and other efficacy measures will be compared in standard care controls (SC) who will receive general diet and physical activity information. The "Improving Autonomic Function and Balance in Diabetic Neuropathy" study is a single blinded, randomized study to determine if an intensive diet and exercise program improves autonomic function and balance. Following baseline testing, participants are randomized to either DPAEP or SC groups. DPAEP participants will receive an intensive physical activity enhancement program with a focus on aerobic activity and a balance program.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 60
• Est. completion date: November 30, 2026
• Est. primary completion date: March 3, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 80 Years

Eligibility

Inclusion Criteria:

• Impaired glucose regulation at the time of screening or within three months of screening. This definition includes patients with IFG, IGT, and early or mild DM2. Patients can be included if they have an increased risk for diabetes with a HBA1C greater than or equal to 5.7% (using a method certified by the National Glycohemoglobin Standardization Program), or they have diabetes with a HBA1C greater than or equal to 6.5%, or an abnormal fasting venous glucose, or abnormal venous glucose values following a 75 gram oral glucose load. Glucose values are as defined (mg/dl): IFG fasting glucose of 100-125 mg/dl, IGT- fasting less than 126, 2 h 140-199, or diabetes - fasting glucose greater than or equal to 126, or 2 h greater than or equal to 200 based on the Standards for Medical Care in Diabetes 2010 by the American Diabetes Association.

• The HbA1c may be normal, but should be less than 9%.

• If diabetic subjects are on medication, they should be stable on medication for at least 3 months prior to entering the study. Addition or change in antidiabetic medication (if on medication) after enrollment does not affect participation or group assignment.

• Impaired glucose regulation is the most likely cause of the neuropathy (determined by a medical history, family history, history of medications, occupational history, history of exposure to toxins (including significant alcohol use), physical and neurological examinations, and appropriate laboratory studies.

• Autonomic neuropathy as defined by the Toronto Diabetic Neuropathy Expert Group 2010/11 consensus criteria. Subjects with be entered into the study if they have (1) increased symptoms of autonomic neuropathy based on an increase in the number of symptoms (>3) OR impact score (>7) in the validated SAS OR (2) at least two abnormalities on autonomic testing. The autonomic testing includes: (a) heart rate variability (E:I ratio and heart rate range-HRR), (b) Valsalva ratio, (c) Valsalva beat to beat blood pressure variation, (d) 30:15 ratio, (e) tilt table testing, and (f) QSART values.

• Age 30 (to exclude patients with type 1 diabetes) to 80 years inclusive

• Medically stable at the time of enrollment.

• Women of childbearing potential must be using an acceptable method of contraception to prevent pregnancy when they are enrolled in the study and must agree to continue to practice an acceptable method of contraception for the duration of their participation in the study.

• Patient must agree to take an alternative medication to coumadin when undergoing a skin biopsy.

Exclusion Criteria:

• Pregnant women, prisoners, institutionalized subjects and other at risk subjects will not be included in this study.

• Neuropathy due to factors other than impaired glucose regulation based on careful clinical and laboratory evaluation by the physician.

• Current severe medical conditions that are active on the day of screening that would affect the patient's ability to participate in or complete the study.

• Autonomic neuropathy that is so severe that it would limit the patient's ability to participate in the study interventions.

Related Conditions & MeSH terms

• Diabetes
• Diabetic Neuropathies
• Glucose Intolerance
• Impaired Glucose Tolerance
• Neuropathy
• Peripheral Nervous System Diseases

Intervention

Behavioral:
• lifestyle modification
Structured weight loss or weight maintenance and aerobic exercise intervention for 12 months or standard of care weight and exercise management

Locations

Country	Name	City	State
United States	Baltimore VA Medical Center VA Maryland Health Care System, Baltimore, MD	Baltimore	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
VA Office of Research and Development

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Sweat gland nerve fiber density	This outcome assesses sweat gland nerve fiber density, which is proposed as a sensitive neuropathy pathology biomarker.	12 months
Primary	Autonomic Function: heart rate variability	This is a cardiac autonomic measure that will be carried out using clinical equipment in the autonomic laboratory at the site. The measurement requires placing electrodes near the heart similar to an EKG.	12 months
Secondary	balance	This outcome measure assesses changes in trunk positioning using a standardized, validated test.	6 and 12 months