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The Health Influences of Puberty (HIP) Study

This study is currently recruiting participants.
Verified January 2013 by University of Colorado, Denver
Sponsor:
Collaborators:
American Diabetes Association
National Institutes of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
University of Colorado, Denver
ClinicalTrials.gov Identifier:
NCT01775813
First received: October 5, 2012
Last updated: January 25, 2013
Last verified: January 2013
History of Changes
  Purpose

The Health Influences of Puberty (HIP) Study is designed to explore the relationships between puberty and the onset of type 2 diabetes in adolescents. The results of this study will help us better understand how to prevent type 2 diabetes in these youth. Children go through many changes during puberty, including important hormonal and behavioral alterations. Among these changes, it has long been known that, during puberty, insulin does not work as well as it does before and after puberty. This is called physiologic insulin resistance. In healthy children, this does not cause diabetes or affect blood sugar in any way because the body is able to compensate by making more insulin. Indeed, this is thought to be an important part of the adolescent growth spurt. However, in some children with increased risk for developing type 2 diabetes due to obesity and genetics, the worsening insulin resistance of puberty cannot be compensated for and these youth get diabetes early. The investigators believe this is because type 2 diabetes is rarely, if ever, seen before puberty begins, and the peak of diabetes onset in adolescents occurs at the time of the worst insulin resistance. This specific research project has two goals: 1. To examine effects of obesity on how well the body's insulin works during puberty, and 2. To see if treatment of obese children during this critical period of puberty with a medication that improves insulin resistance (metformin) will help prevent early onset type 2 diabetes.


Condition Intervention Phase
Obesity
Insulin Resistance
Gonadal Dysfunction
Type 2 Diabetes
 Drug: Metformin
 Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Combined Influence of Puberty and Obesity on Insulin Resistance in Adolescents

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by University of Colorado, Denver:

Primary Outcome Measures:
  • Change in insulin sensitivity [ Time Frame: Baseline, Tanner (puberty) stage 4-average 1.5 years from baseline, Tanner (puberty) stage 5-average 2.5 yrs from baseline, 6 mos post-treatment-average 3 yrs from baseline ] [ Designated as safety issue: No ]
    As measured by in intravenous glucose tolerance test (IVGTT). Patients are randomized to receive metformin or placebo at Tanner stage 2-3 of puberty. They are reassessed at Tanner 4 and again at Tanner 5. At that point, the treatment is stopped and they are reassessed 6 months after stopping treatment to see if effects of treatment persist.


Secondary Outcome Measures:
  • Change in insulin secretion [ Time Frame: Baseline, Tanner (puberty) stage 4-average 1.5 years from baseline, Tanner (puberty) stage 5-average 2.5 yrs from baseline, 6 mos post-treatment-average 3 yrs from baseline ] [ Designated as safety issue: No ]
    As measured by IVGTT. Please see primary outcome for more detail about timing of measurement.

  • Change in disposition index [ Time Frame: Baseline, Tanner (puberty) stage 4-average 1.5 years from baseline, Tanner (puberty) stage 5-average 2.5 yrs from baseline, 6 mos post-treatment-average 3 yrs from baseline ] [ Designated as safety issue: No ]
    Please see primary outcome for more detail about timing of measurement.

  • Change in lipid measures [ Time Frame: Baseline, Tanner (puberty) stage 4-average 1.5 years from baseline, Tanner (puberty) stage 5-average 2.5 yrs from baseline, 6 mos post-treatment-average 3 yrs from baseline ] [ Designated as safety issue: No ]
    Please see primary outcome for more detail about timing of measurement.

  • Change in insulin-like growth factor 1 [ Time Frame: Baseline, Tanner (puberty) stage 4-average 1.5 years from baseline, Tanner (puberty) stage 5-average 2.5 yrs from baseline ] [ Designated as safety issue: No ]
  • Change in testosterone [ Time Frame: Baseline, Tanner (puberty) stage 4-average 1.5 years from baseline, Tanner (puberty) stage 5-average 2.5 yrs from baseline ] [ Designated as safety issue: No ]
  • Change in estradiol [ Time Frame: Baseline, Tanner (puberty) stage 4-average 1.5 years from baseline, Tanner (puberty) stage 5-average 2.5 yrs from baseline ] [ Designated as safety issue: No ]
  • Change in sex hormone binding globulin [ Time Frame: Baseline, Tanner (puberty) stage 4-average 1.5 years from baseline, Tanner (puberty) stage 5-average 2.5 yrs from baseline ] [ Designated as safety issue: No ]
  • Change in dehydroepiandrosterone sulfate [ Time Frame: Baseline, Tanner (puberty) stage 4-average 1.5 years from baseline, Tanner (puberty) stage 5-average 2.5 yrs from baseline ] [ Designated as safety issue: No ]
  • Change in interleukin-6 [ Time Frame: Baseline, Tanner (puberty) stage 4-average 1.5 years from baseline, Tanner (puberty) stage 5-average 2.5 yrs from baseline ] [ Designated as safety issue: No ]
  • Change in high Sensitivity C-reactive protein [ Time Frame: Baseline, Tanner (puberty) stage 4-average 1.5 years from baseline, Tanner (puberty) stage 5-average 2.5 yrs from baseline ] [ Designated as safety issue: No ]
  • Change in aspartate Aminotransferase (AST) [ Time Frame: Baseline, Tanner (puberty) stage 4-average 1.5 years from baseline, Tanner (puberty) stage 5-average 2.5 yrs from baseline ] [ Designated as safety issue: No ]
  • Change in alanine transaminase (ALT) [ Time Frame: Baseline (Tanner 2-3), Tanner 4, Tanner 5 ] [ Designated as safety issue: No ]
  • Change in urinary Luteinizing hormone [ Time Frame: Baseline, every 6 months during the trial, Final visit (average 3 yrs after baseline) ] [ Designated as safety issue: No ]
  • Change in urinary Follicle-stimulating hormone [ Time Frame: Baseline, every 6 months during the trial, Final visit-average 3 yrs after baseline ] [ Designated as safety issue: No ]
  • Change in urinary estradiol metabolites [ Time Frame: Baseline, every 6 months during the trial, Final visit-average 3 yrs after baseline ] [ Designated as safety issue: No ]
  • Change in hemoglobin A1c [ Time Frame: Baseline, Tanner (puberty) stage 4-average 1.5 years from baseline, Tanner (puberty) stage 5-average 2.5 yrs from baseline ] [ Designated as safety issue: No ]
  • Change in leptin [ Time Frame: Baseline, Tanner (puberty) stage 4-average 1.5 years from baseline, Tanner (puberty) stage 5-average 2.5 yrs from baseline ] [ Designated as safety issue: No ]
  • Change in %body fat [ Time Frame: Baseline, Tanner (puberty) stage 4-average 1.5 years from baseline, Tanner (puberty) stage 5-average 2.5 yrs from baseline ] [ Designated as safety issue: No ]
  • Change in visceral adipose [ Time Frame: Baseline, Tanner (puberty) stage 4-average 1.5 years from baseline, Tanner (puberty) stage 5-average 2.5 yrs from baseline ] [ Designated as safety issue: No ]
    Measured in a subset (10 per group) by single slice MRI

  • Change in liver adipose [ Time Frame: Baseline, Tanner (puberty) stage 4-average 1.5 years from baseline, Tanner (puberty) stage 5-average 2.5 yrs from baseline ] [ Designated as safety issue: No ]
    Measured in a subset (10 per group) by fast MRI technique


Estimated Enrollment: 156
Study Start Date: June 2011
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Metformin
Dosage form: Metformin 1000 mg tablets Dosage: 1000 mg by mouth twice daily Duration: From early puberty (Tanner 3-4) until puberty completion (Tanner 5), approximately 3 years
 Drug: Metformin
After randomization, the study drug (metformin or placebo) is gradually titrated to full dose of 1000 mg BID (or to maximum tolerated, at least 500 mg BID) over a period of 4 weeks to minimize adverse gastrointestinal effects. Participants are seen every three months to measure compliance and dispense new study drug. Every 6 months, they also have a physical examination in order to determine puberty staging. Study measurements (IVGTT, bloodwork, DXA) are performed at Tanner 4 puberty and Tanner 5 (puberty completion), at which time the study drug is stopped. Study measurements will be performed again 6 months after study drug is completed to assess if effects are persistent after study drug is stopped. During the treatment period, all participants receive standard lifestyle counseling.
Other Names:
  • Glucophage
  • Glumetza
  • Fortamet
  • Riomet
Placebo Comparator: Sugar pill
Dosage form: Stamped placebo pill to look like the 1000 mg metformin pill Dosage: 1 pill taken orally twice daily Duration: From early puberty (Tanner 3-4) until puberty completion (Tanner 5), approximately 3 years

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   9 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • BMI ≥ 95th percentile
  • At least Tanner 2, but no more than Tanner 3
  • Age ≥ 9 years
  • Absence of impaired glucose tolerance (IGT), impaired fasting glucose (IFG) or Type 2 diabetes mellitus (T2DM)

Exclusion Criteria:

  • Presence of T2DM, IGT or IFG
  • Any disorder or medication known to effect glucose tolerance;
  • Hypertension or hyperlipidemia requiring pharmacological intervention;
  • Weight >300lbs. due to limits of imaging tables.
  • Chronic illness
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01775813

Contacts
Contact: Allison Hilkin, BS 720-777-6148 Allison.Hilkin@childrenscolorado.org
Contact: Megan Kelsey, MD, MS 720-777-6138 Megan.Kelsey@childrenscolorado.org

Locations
United States, Colorado
Children's Hospital Colorado Recruiting
Aurora, Colorado, United States, 80045
Principal Investigator: Megan Kelsey, MD, MS            
Sponsors and Collaborators
University of Colorado, Denver
American Diabetes Association
National Institutes of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Investigators
Principal Investigator: Megan Kelsey, MD, MS University of Colorado Denver/Children's Hospital Colorado
  More Information

No publications provided

Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT01775813     History of Changes
Other Study ID Numbers: 07-0988, Protocol 914, 1-11-JF-23, 5K12HD057022
Study First Received: October 5, 2012
Last Updated: January 25, 2013
Health Authority: United States: Data and Safety Monitoring Board
United States: Institutional Review Board
United States: Federal Government

Keywords provided by University of Colorado, Denver:
Insulin resistance
Puberty
Obesity
 Hypogonadism
Gonadal dysfunction
Metformin

Additional relevant MeSH terms:
Diabetes Mellitus, Type 2
Gonadal Disorders
Insulin Resistance
Obesity
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Hyperinsulinism
 Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 21, 2013