INMED: Improving Neuropathy and Mobility in People With Early Diabetes

• Sponsor: VA Office of Research and Development (U.S. Fed)
• Overall Status: Completed
• CT.gov ID: NCT00780559
• Collaborator: University of Maryland, College Park (Other), University of Michigan (Other)
• Enrollment: 72
• Locations: 3
• Arms: 2
• Actual Duration (Months): 99.3
• Patients Per Site: 24
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to determine if an individually tailored diet and physical enhancement program can improve mobility, physical activity, and neuropathy in people with early diabetes.

Condition or Disease	Intervention/Treatment	Phase
Diabetes; Physical Activity	Behavioral: Tailored Diet and Physical Activity; Behavioral: Standard of Care	N/A

Detailed Description

Neuropathy is the most common complication of diabetes mellitus. Impaired glucose regulation (IGR) is associated with development of peripheral neuropathy coupled with gait and mobility impairment that may be disabling for the patient. Recent novel data from the investigators' group indicates that improved diet and exercise can significantly improve and even reverse neuropathy associated with IGR, however this has not been tested as a specific intervention in a controlled diabetes complications trial. IGR includes patients with early type 2 diabetes mellitus (T2DM), impaired glucose tolerance (IGT), and impaired fasting glucose (IFG) based on standardized criteria for the diagnosis of T2DM. The investigators hypothesize that, compared to IGR participants advised to follow the current standard care recommendations on diet and exercise (Standard Care or "SC"), IGR participants undergoing a Tailored Diet and Physical Activity (TDPA) enhancement program will show greater improvement in the 6 minute walk test (6MW) and will show a greater reduction in markers of neuropathy progression e.g. intraepidermal nerve fiber density (IEFND). Furthermore, the investigators will test the hypothesis that improvement in measures of neuropathy, mobility function and physical activity (PA) will correlate strongly with each other and with improvement in specific measures of metabolic function, and weight loss. This proposal will permit us to determine if TDPA can improve mobility and induce nerve regeneration in subjects with early diabetes.

Study Design

• Study Type: Interventional
• Actual Enrollment: 72 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: parallel treatmentsparallel treatments
• Masking: Double (Participant, Investigator)
• Masking Description: double blind
• Primary Purpose: Treatment
• Official Title: Improving Neuropathy and Mobility in Subjects With Early Diabetes
• Actual Study Start Date: Nov 1, 2009
• Actual Primary Completion Date: Dec 31, 2017
• Actual Study Completion Date: Feb 8, 2018

Arms and Interventions

Arm	Intervention/Treatment
Other: Tailored Diet and Physical Activity Subjects will receive an individually tailored diet and physical activity enhancement program	Behavioral: Tailored Diet and Physical Activity; Subjects will receive an individually tailored diet and physical activity enhancement program
Other: Standard of Care Subjects will be told to reduce their baseline weight by 7% and exercise for 150 minutes/week. There is no tailored, directed program.	Behavioral: Standard of Care; Subjects will be told to reduce their baseline weight by 7% and exercise for 150 minutes/week. There is no tailored, directed program.

Outcome Measures

Primary Outcome Measures

1. Six Minute Walk (6MW) Test [Six Months]

   Measures distance covered by participant when walking at a brisk pace without running for six minutes in feet.

2. Change in 6-Minute-Walk Test Measured in Feet Between Baseline and 12 Months [Baseline and 12 Months]

Secondary Outcome Measures

1. Intraepidermal Nerve Fiber Density (Distal Leg) [12 Months]

   Measure of the number of skin fibers/mm in the lower extremity (distal leg) at 12 months

2. Intraepidermal Nerve Fiber Density (IENFD) at the Proximal Thigh [12 Months]

   Measure of the number of skin fibers/mm in the lower extremity (proximal thigh) at 12 months

Other Outcome Measures

1. Change in Physical Activity (PA) at 12 Months as Measured by the CHAMPS (Community Health Activities Model Program for Seniors) Activity Scale [Baseline and 12 Months]

   Physical Activity measured by CHAMPS provides an estimated caloric expenditure of subject based on weight and weekly physical activity, as assessed by the questionnaire. Change in physical activity is determined by the difference in daily caloric expenditure at baseline and 12 months.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 30 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

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

• The HbA1c may be normal, but must be <8%.

• 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 medications after enrollment does not affect participation or group assignment.

• No risk factors for other causes for neuropathy (determined by a medical history, family history, history of medications, occupational history, history of exposure to toxins, physical and neurological examinations, and laboratory studies).

• Clinical signs or symptoms of neuropathy as determined by the treating neurologists history and physical exam, plus an abnormality of one of the following: nerve conduction studies (NCS), Quantitative Sudomotor Autonomic Reflex Testing (QSART), Quantitative Sensory Testing (QST), or IENFD.

• Age range from 30 to 80 years inclusive at the time of screening

• Medically stable at the time of enrollment.

• Able to participate in a standing exercise program without constant standby monitoring.

• 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 taking an alternative medication to coumadin when undergoing a skin biopsy

• Willing to complete weekly self-report questionnaires.

• Willing to accept assignment to either training group.

• Willing and able to increase activity level and exercise independently at home.

Exclusion Criteria:

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

• Taking insulin.

• Etiology of sensorimotor neuropathy other than IGR based on careful clinical and laboratory evaluation.

• Current severe medical conditions that are active on the day of enrollment and would affect a patient's ability to complete study. This may include active advanced current ischemic heart disease (e.g., angina or congestive heart failure), permanent residual lower extremity weakness or loss of balance resulting from a stroke, active severe obstructive or restrictive pulmonary disease, ongoing cancer treatment, renal failure currently requiring dialysis, or severe ongoing peripheral vascular disease.

• An inability to understand or cooperate with the procedures of the trial or refusal to sign the informed consent.

• Patients who are unable to answer questions correctly on the Evaluation to Sign Consent (ESC) tool.

• Significant other neurologic, rheumatological, neuromuscular, or other extremity conditions that limit safe exercise or weight bearing.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Maryland	Baltimore	Maryland	United States	20742
2	Baltimore VA Medical Center VA Maryland Health Care System, Baltimore, MD	Baltimore	Maryland	United States	21201
3	VA Ann Arbor Healthcare System, Ann Arbor, MI	Ann Arbor	Michigan	United States	48105

Sponsors and Collaborators

• VA Office of Research and Development
• University of Maryland, College Park
• University of Michigan

Investigators

• Principal Investigator: James W Russell, MD, Baltimore VA Medical Center VA Maryland Health Care System, Baltimore, MD

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Sep 9, 2010

More Information

Publications

None provided.

• Responsible Party: VA Office of Research and Development
• ClinicalTrials.gov Identifier: NCT00780559
• Other Study ID Numbers: B6017-R; INMED 42940
• First Posted: Oct 27, 2008
• Last Update Posted: Apr 9, 2021
• Last Verified: Mar 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by VA Office of Research and Development: Neuropathy; diabetes
• Additional relevant MeSH terms: Diabetes Mellitus

Study Results

Participant Flow

Pre-assignment Detail	Participants were excluded from the study prior to assignment for groups (n=12) due to failure of screening (e.g. not meeting inclusion/exclusion criteria, n=10) or declined to participate (n=2.)

Arm/Group Title	Tailored Diet and Physical Activity	Standard of Care
Arm/Group Description	Tailored Diet and Physical Activity: Subjects will receive an individually tailored diet and physical activity enhancement program	Standard of Care: Subjects will be told to reduce their baseline weight by 7% and exercise for 150 minutes/week. There is no tailored, directed program.
Period Title: Overall Study
STARTED	32	40
COMPLETED	29	33
NOT COMPLETED	3	7

Baseline Characteristics

Arm/Group Title	Tailored Diet and Physical Activity	Standard of Care	Total
Arm/Group Description	Subjects will receive an individually tailored diet and physical activity enhancement program	Subjects will be told to reduce their baseline weight by 7% and exercise for 150 minutes/week. There is no tailored, directed program.	Total of all reporting groups
Overall Participants	32	40	72
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	18 56.3%	28 70%	46 63.9%
>=65 years	14 43.8%	12 30%	26 36.1%
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	61.81 (8.25)	61.03 (7.83)	61.38 (7.91)
Sex: Female, Male (Count of Participants)
Female	11 34.4%	13 32.5%	24 33.3%
Male	21 65.6%	27 67.5%	48 66.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	1 2.5%	1 1.4%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	5 15.6%	7 17.5%	12 16.7%
White	26 81.3%	30 75%	56 77.8%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	1 3.1%	2 5%	3 4.2%
BMI (Body Mass Index), Categorical (Count of Participants)
BMI < 30 kg/m^2	13 40.6%	19 47.5%	32 44.4%
BMI 30 - 40 kg/m^2	12 37.5%	19 47.5%	31 43.1%
BMI > 40 kg/m^2	7 21.9%	2 5%	9 12.5%
BMI (Body Mass Index), Continuous (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	33.21 (7.65)	30.83 (7.06)	31.89 (7.37)

Outcome Measures

1. Primary Outcome

Title	Six Minute Walk (6MW) Test
Description	Measures distance covered by participant when walking at a brisk pace without running for six minutes in feet.
Time Frame	Six Months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tailored Diet and Physical Activity	Standard of Care
Arm/Group Description	Subjects will receive an individually tailored diet and physical activity enhancement program	Subjects will be told to reduce their baseline weight by 7% and exercise for 150 minutes/week. There is no tailored, directed program.
Measure Participants	32	40
Least Squares Mean (Standard Error) [feet]	156.644156 (35.364227)	61.257846 (35.840649)

2. Primary Outcome

Title	Change in 6-Minute-Walk Test Measured in Feet Between Baseline and 12 Months
Time Frame	Baseline and 12 Months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tailored Diet and Physical Activity	Standard of Care
Arm/Group Description	Tailored Diet and Physical Activity: Subjects will receive an individually tailored diet and physical activity enhancement program	Standard of Care: Subjects will be told to reduce their baseline weight by 7% and exercise for 150 minutes/week. There is no tailored, directed program.
Measure Participants	32	40
Least Squares Mean (Standard Error) [feet]	188.415845 (34.346235)	100.559319 (36.399507)

3. Secondary Outcome

Title	Intraepidermal Nerve Fiber Density (Distal Leg)
Description	Measure of the number of skin fibers/mm in the lower extremity (distal leg) at 12 months
Time Frame	12 Months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tailored Diet and Physical Activity	Standard of Care
Arm/Group Description	Tailored Diet and Physical Activity: Subjects will receive an individually tailored diet and physical activity enhancement program	Standard of Care: Subjects will be told to reduce their baseline weight by 7% and exercise for 150 minutes/week. There is no tailored, directed program.
Measure Participants	32	40
Least Squares Mean (Standard Error) [fibers/mm]	1.28627099 (0.81830712)	-0.38943425 (0.84781677)

4. Secondary Outcome

Title	Intraepidermal Nerve Fiber Density (IENFD) at the Proximal Thigh
Description	Measure of the number of skin fibers/mm in the lower extremity (proximal thigh) at 12 months
Time Frame	12 Months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tailored Diet and Physical Activity	Standard of Care
Arm/Group Description	Tailored Diet and Physical Activity: Subjects will receive an individually tailored diet and physical activity enhancement program	Standard of Care: Subjects will be told to reduce their baseline weight by 7% and exercise for 150 minutes/week. There is no tailored, directed program.
Measure Participants	32	40
Least Squares Mean (Standard Error) [fibers/mm]	1.53825016 (0.83395303)	-0.54419990 (0.87926529)

5. Other Pre-specified Outcome

Title	Change in Physical Activity (PA) at 12 Months as Measured by the CHAMPS (Community Health Activities Model Program for Seniors) Activity Scale
Description	Physical Activity measured by CHAMPS provides an estimated caloric expenditure of subject based on weight and weekly physical activity, as assessed by the questionnaire. Change in physical activity is determined by the difference in daily caloric expenditure at baseline and 12 months.
Time Frame	Baseline and 12 Months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tailored Diet and Physical Activity	Standard of Care
Arm/Group Description	Tailored Diet and Physical Activity: Subjects will receive an individually tailored diet and physical activity enhancement program	Standard of Care: Subjects will be told to reduce their baseline weight by 7% and exercise for 150 minutes/week. There is no tailored, directed program.
Measure Participants	32	40
Least Squares Mean (Standard Error) [kcal/day]	-735.249060 (886.986000)	296.998122 (937.935990)

Adverse Events

Time Frame	Adverse event data for each participant was collected over one year per study patient, or the duration of the study for each participant.
Adverse Event Reporting Description	The definition of adverse events and/or serious adverse events does not differ from that which is listed here on clinicaltrials.gov. Adverse Events were collected from patient reports and phone call follow-ups.
Arm/Group Title	Tailored Diet and Physical Activity		Standard of Care
Arm/Group Description	Subjects will receive an individually tailored diet and physical activity enhancement program		Subjects will be told to reduce their baseline weight by 7% and exercise for 150 minutes/week. There is no tailored, directed program.
All Cause Mortality
	Tailored Diet and Physical Activity		Standard of Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/32 (3.1%)		0/40 (0%)
Serious Adverse Events
	Tailored Diet and Physical Activity		Standard of Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/32 (0%)		0/40 (0%)
Other (Not Including Serious) Adverse Events
	Tailored Diet and Physical Activity		Standard of Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/32 (3.1%)		0/40 (0%)
Product Issues
Skin Irritation	1/32 (3.1%)	1	0/40 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.