Pathobiology and Reversibility of Prediabetes in a Biracial Cohort (PROP-ABC)

This study is enrolling participants by invitation only.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Tennessee
ClinicalTrials.gov Identifier:
NCT02027571
First received: January 2, 2014
Last updated: January 3, 2014
Last verified: January 2014
  Purpose

The reasons for the epidemics of diabetes and prediabetes, and why individuals from certain populations suffer at higher rates are not well known. In the Pathobiology and Reversibility of Prediabetes in a Biracial Cohort (PROP-ABC) study, nearly 400 African Americans and Caucasians whose parents have type 2 diabetes will undergo repeated testing to determine what factors lead to the occurrence of prediabetes, and whether race still plays a major role in a setting where everyone being studied has one or both parents with diabetes. The PROP-ABC Study also will test the hypothesis that the ability of intensive lifestyle intervention to reverse prediabetes and return people's metabolism back to normal is dependent on how long people have had prediabetes.


Condition Intervention
Prediabetes
Type 2 Diabetes
Obesity
Behavioral: Intensive Lifestyle Intervention (ILI)

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Pathobiology and Reversibility of Prediabetes in a Biracial Cohort (PROP-ABC)

Resource links provided by NLM:


Further study details as provided by University of Tennessee:

Primary Outcome Measures:
  • The primary outcome measure is restoration of normal glucose regulation [ Time Frame: Up to 60 months ] [ Designated as safety issue: No ]
    The primary outcome measure is restoration of normal glucose regulation (FPG <100 mg/dl and 2hrPG < 140 mg/dl).


Secondary Outcome Measures:
  • Glucose normalization [ Time Frame: Up to 60 months ] [ Designated as safety issue: No ]
    Secondary endpoints include normalization of either fasting plasma glucose or 2-hr OGTT plasma glucose levels, occurrence of diabetes, insulin sensitivity and secretion.


Other Outcome Measures:
  • Incident prediabetes in observational cohort [ Time Frame: Up to 60 months ] [ Designated as safety issue: No ]
    Incident prediabetes, microvascular complications, endothelial function, ankle-brachial index, body composition, adiposity measures, FPG, 2hPG , A1c, adipo- and inflammatory cytokines (hsCRP, TNF-a, IL-1a, IL-6, resistin, leptin and adiponectin), metabolic syndrome and individual components (waist, BP, triglycerides, HDL cholesterol, FPG), metabolically healthy and unhealthy obese phenotypes, transaminases (surrogate for liver fat), diet (FHQ score) physical activity (MAQ and NHANES scores) and smoking history.


Estimated Enrollment: 300
Study Start Date: October 2013
Estimated Study Completion Date: October 2018
Estimated Primary Completion Date: October 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Intensive Lifestyle Intervention (ILI)
ILI consists of weight loss ( > 10%); caloric reduction; physical activity (180 min/week); monthly visits for group counseling for 6 months, followed by quarterly visits; and meal replacements.
Behavioral: Intensive Lifestyle Intervention (ILI)
ILI consists of weight loss ( > 10%); caloric reduction; physical activity (180 min/week); monthly visits for group counseling for 6 months, followed by quarterly visits; and meal replacements.

Detailed Description:

The Pathobiology and Reversibility of Prediabetes in a Biracial Cohort (PROP-ABC) study is following an extant cohort of 376 initially normoglycemic African American and Caucasian offspring of parents with type 2 diabetes for an additional 5years. The subjects were enrolled between 2006 and 2009 and have been followed up to 2012, during which 10 have developed diabetes and 101 developed prediabetes, without evidence of racial disparities.

The objectives of PROP-ABC are to gain a fuller understanding of the natural history and predictors of early glucose abnormalities, determine the role of race during the second wave of glycemic progression, and to access the time dependency of reversibility of prediabetes. The study tests 4 hypotheses: 1) Among offspring of parents with type 2 diabetes, early progression from normal to impaired glucose regulation (within 5 yr) occurs in the highest-risk subjects independently of race, whereas late progression (5-10 yr) displays racial disparities, and is predicted by physiological, biochemical and behavioral markers; 2) Early microvascular complications, peripheral vascular disease (PVD), and endothelial dysfunction manifest during transition from normal to impaired glucose regulation, display racial disparities, and are predicted by glycemic and nonglycemic factors; 3) The "metabolically healthy" insulin-sensitive obese (ISO) phenotype displays racial disparities in its association with cardiometabolic risk factors and incident dysglycemia among African-Americans and Caucasians offspring of parents with type 2 diabetes; and 4) Duration of the prediabetic state is a major determinant of, and is inversely related to, the efficacy of lifestyle intervention to induce regression of the prediabetic phenotype and restoration of normal glucose regulation. Participants with prediabetes and others who develop prediabetes during PROP-ABC will receive Intensive Lifestyle intervention (ILI).

We define duration of prediabetes as the interval from date of confirmed prediabetes to the date of initiation of ILI, stratified to 3 prediabetes intervals: a) <1 yr, b) 1 to <3 yr, c) 3-6 yr. The primary outcome measure is restoration of normal glucose regulation (FPG <100 mg/dl and 2hrPG < 140 mg/dl). Secondary endpoints include normalization of either FPG or 2-hrPG, occurrence of diabetes, insulin sensitivity and secretion. Data will be analyzed according to the "intention to treat" principle. Based on power calculations, a sample size of 150 subjects (50/prediabetes interval) would allow detection of medium to large effect off ILI with ~85% power. Kaplan-Meier survival curves will be generated for the 3 prediabetes intervals, and log-rank test will be used to analyze the time to occurrence of primary outcome. The prospective PROP-ABC, designed to identify new cases of prediabetes as they occur, is uniquely placed to test the time dependency of reversibility of incident prediabetes.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • As planned these studies will enroll interested persons from among the group of 376 subjects who participated in the Pathobiology of Prediabetes in a Biracial Cohort (POP-ABC) study between 2006 and 2012. That group includes 267 women and 109 men; 217 are African Americans and 159 are Caucasians. At the time of initial enrollment into POP-ABC, these participants were selected for being nondiabetic offspring of parents with type 2 diabetes. Race and ethnicity was by self-report of non-Hispanic white or non-Hispanic black heritage, and their age range was 18-65 years at enrollment. No new subjects will be recruited into this established cohort. To be eligible for inclusion in the renewal study, subjects must be ambulatory, be in good general health, and must not be taking medications known to alter insulin sensitivity, insulin secretion, or body weight.

Exclusion Criteria:

  • Exclusion criteria: Persons not enrolled in POP-ABC study; diagnosis of diabetes or use of any antidiabetic medication; medical conditions that preclude participation in physical activity; history of liposuction, surgical weight reduction; use of glucocorticoids, beta-blockers, thiazide diuretics (> 25 mg/day), or medication known to alter glucose metabolism. Women who are pregnant or become pregnant while participating in this study will have all testing procedures delayed until 12 months after delivery.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT02027571

Locations
United States, Tennessee
Clinical Research Center, University of Tennessee Health Scienc Ctr
Memphis, Tennessee, United States, 38104
Sponsors and Collaborators
University of Tennessee
Investigators
Principal Investigator: Samuel Dagogo-Jack, MD University of Tennessee Health Science Center
  More Information

Publications:
Responsible Party: University of Tennessee
ClinicalTrials.gov Identifier: NCT02027571     History of Changes
Other Study ID Numbers: IRB Number: 12-01970-FB, 2R01DK067269-06A1
Study First Received: January 2, 2014
Last Updated: January 3, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Tennessee:
Diabetes
Race/Ethnicity
Offspring Cohort
African Americans
Prediabetes Reversal
Lifestyle Intervention
Insulin Sensitivity
Beta-cell Function
Diabetes Prevention

Additional relevant MeSH terms:
Glucose Intolerance
Prediabetic State
Diabetes Mellitus
Diabetes Mellitus, Type 2
Obesity
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms
Hyperglycemia

ClinicalTrials.gov processed this record on August 27, 2014