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The Health Influences of Puberty (HIP) Study (HIP)

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ClinicalTrials.gov Identifier: NCT01775813
Recruitment Status : Completed
First Posted : January 25, 2013
Last Update Posted : July 17, 2018
Sponsor:
Collaborators:
American Diabetes Association
National Institutes of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Children's Hospital Colorado
Information provided by (Responsible Party):
University of Colorado, Denver

Brief Summary:
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 or disease Intervention/treatment Phase
Obesity Insulin Resistance Gonadal Dysfunction Type 2 Diabetes Drug: Metformin Phase 4

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 77 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Combined Influence of Puberty and Obesity on Insulin Resistance in Adolescents
Actual Study Start Date : June 2011
Actual Primary Completion Date : May 31, 2018
Actual Study Completion Date : May 31, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Puberty

Arm Intervention/treatment
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
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




Primary Outcome Measures :
  1. 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 ]
    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 :
  1. 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 ]
    As measured by IVGTT. Please see primary outcome for more detail about timing of measurement.

  2. 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 ]
    Please see primary outcome for more detail about timing of measurement.

  3. 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 ]
    Please see primary outcome for more detail about timing of measurement.

  4. 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 ]
    IGF-1 measured in serum at each time point

  5. 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 ]
    Testosterone measured in serum at each time point

  6. 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 ]
    Estradiol measured in serum at each time point

  7. 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 ]
    SHBG measured in serum at each time point

  8. 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 ]
    DHEA-S measured in serum at each time point

  9. 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 ]
    IL-6 measured in serum at each time point.

  10. 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 ]
    hsCRP measured in serum at each time point

  11. 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 ]
    AST measured in serum at each time point

  12. Change in alanine transaminase (ALT) [ Time Frame: Baseline (Tanner 2-3), Tanner 4, Tanner 5 ]
    ALT measured in serum at each time point

  13. Change in urinary Luteinizing hormone [ Time Frame: Baseline, every 6 months during the trial, Final visit (average 3 yrs after baseline) ]
    LH measured in an overnight urine sample at time points below

  14. Change in urinary Follicle-stimulating hormone [ Time Frame: Baseline, every 6 months during the trial, Final visit-average 3 yrs after baseline ]
    FSH measured in overnight urine sample at time points below

  15. Change in urinary estradiol metabolites [ Time Frame: Baseline, every 6 months during the trial, Final visit-average 3 yrs after baseline ]
    estradiol metabolite (E1c) measured in an overnight urine sample at each time point

  16. 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 ]
    HbA1c measured by HPLC at time points below

  17. 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 ]
    Leptin measured in serum at time points below

  18. 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 ]
    % body fat measured by DXA at time points below

  19. 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 ]
    Measured in a subset (10 per group) by single slice MRI

  20. 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 ]
    Measured in a subset (10 per group) by fast MRI technique



Information from the National Library of Medicine

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Ages Eligible for Study:   9 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01775813


Locations
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United States, Colorado
Children's Hospital Colorado
Aurora, Colorado, United States, 80045
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)
Children's Hospital Colorado
Investigators
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Principal Investigator: Megan Kelsey, MD, MS University of Colorado Denver/Children's Hospital Colorado

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Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT01775813     History of Changes
Other Study ID Numbers: 07-0988
Protocol 914 ( Other Identifier: Children's Hospital Colorado )
1-11-JF-23 ( Other Grant/Funding Number: American Diabetes Association )
5K12HD057022 ( U.S. NIH Grant/Contract )
First Posted: January 25, 2013    Key Record Dates
Last Update Posted: July 17, 2018
Last Verified: July 2018

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

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