RISE Pediatric Medication Study (RISE Peds)

This study is currently recruiting participants.
Verified December 2013 by RISE Study Group
Sponsor:
Collaborator:
Information provided by (Responsible Party):
RISE Study Group
ClinicalTrials.gov Identifier:
NCT01779375
First received: January 28, 2013
Last updated: December 19, 2013
Last verified: December 2013
  Purpose

The RISE Pediatric Medication Study is a 2-arm, 4-center, clinical trial of children with prediabetes and early type 2 diabetes to address the hypothesis that aggressive glucose lowering will lead to recovery of beta-cell function that will be sustained after withdrawal of treatment. Pediatric participants (ages 10-19) will be randomized to one of the following treatment regimens: (1) metformin alone or (2) early intensive treatment with basal insulin glargine followed by metformin.

The primary clinical question RISE will address is: Are improvements in ß-cell function following 12 months of active treatment maintained for 3 months following the withdrawal of therapy? Secondary outcomes will assess durability of glucose tolerance following withdrawal of therapy, and whether biomarkers obtained in the fasting state predict parameters of ß-cell function, insulin sensitivity and glucose tolerance and the response to an intervention.


Condition Intervention Phase
Prediabetes
Type 2 Diabetes
Drug: Metformin
Drug: Glargine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Restoring Insulin Secretion Pediatric Medication Study

Resource links provided by NLM:


Further study details as provided by RISE Study Group:

Primary Outcome Measures:
  • ß-cell function measured by hyperglycemic clamp techniques [ Time Frame: 3-months after a medication washout ] [ Designated as safety issue: No ]
    Participants will have 12-months of active therapy and 3-months of washout after which the primary outcome will be assessed.


Secondary Outcome Measures:
  • Hyperglycemic clamp and oral glucose tolerance test (OGTT) measures of ß-cell Function and Glucose Tolerance [ Time Frame: 3-months after a medication washout ] [ Designated as safety issue: No ]
    Measures derived from the hyperglycemic clamp that are not specified as primary outcomes and measures derived from the OGTT.


Other Outcome Measures:
  • Hyperglycemic clamp and OGTT measures of ß-cell Function and Glucose Tolerance [ Time Frame: After 12 months of active treatment ] [ Designated as safety issue: No ]
    Measures derived from the hyperglycemic clamp and the OGTT related to treatment effect at the end of the 12 month active intervention period compared to pre-treatment baseline.


Estimated Enrollment: 90
Study Start Date: April 2013
Estimated Study Completion Date: August 2017
Estimated Primary Completion Date: August 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Metformin alone
Metformin will be titrated to the maximum dose tolerated (up to 2000 mg/day).
Drug: Metformin
Other Name: Glucophage
Active Comparator: Glargine followed by Metformin
Basal insulin glargine for 3 months titrated to achieve a morning fasting blood glucose of 85-95 mg/dl, followed by metformin (titrated up to 2000 mg/day) for 9 months.
Drug: Metformin
Other Name: Glucophage
Drug: Glargine
Other Name: Insulin glargine, Lantus

  Eligibility

Ages Eligible for Study:   10 Years to 19 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Fasting plasma glucose ≥90 mg/dl plus 2-hour glucose ≥140 mg/dl on 75 gm OGTT plus laboratory-based HbA1c ≥5.8 and ≤8.0% if treatment naïve. There is no upper limit for the 2-hour glucose on OGTT. In those taking metformin laboratory-based HbA1c must be ≤7.5% if on metformin for <3 months and ≤7.0% if on metformin for 3-6 months.
  2. Age 10-19 years
  3. Pubertal development Tanner stage >1 as defined by breast stage >1 in girls, and testes >3 cc's in boys.
  4. Body mass index (BMI) ≥85th percentile but ≤50 kg/m2
  5. Self-reported diabetes <6 months in duration
  6. Treatment with metformin for <6 months preceding screening

Exclusion Criteria:

  1. Underlying disease likely to limit life span and/or increase risk of intervention or an underlying condition that is likely to limit ability to participate in outcomes assessment
  2. An underlying disease that affects glucose metabolism other than type 2 diabetes mellitus
  3. Taking medications that affect glucose metabolism, or has an underlying condition that is likely to require such medications
  4. Treatment with insulin for >1 week preceding screening
  5. Active infections
  6. Renal disease (serum creatinine >1.2 mg/dl) or serum potassium abnormality (<3.4 or >5.5 mmol/l)
  7. Anemia (hemoglobin <11 g/dl in girls, <12 g/dl in boys) or known coagulopathy
  8. Cardiovascular disease, including uncontrolled hypertension defined as average systolic or diastolic blood pressure > 99 percentile for age or >135/90, despite adequately prescribed antihypertensive medications. Participants must be able to safely tolerate administration of intravenous fluids required during clamp studies.
  9. History of conditions that may be precipitated or exacerbated by a study drug:

    1. Serum alanine transaminase (ALT) more than 3 times the upper limit of normal
    2. Excessive alcohol intake
    3. Sub-optimally treated thyroid disease
  10. Conditions or behaviors likely to affect the conduct of the RISE Study

    1. Participant and/or parents unable or unwilling to give informed consent
    2. Participant and/or parents unable to adequately communicate with clinic staff
    3. Another household member is a participant or staff member in RISE
    4. Current, recent or anticipated participation in another intervention research project that would interfere with any of the interventions/outcomes in RISE
    5. Weight loss of ≥5% of body weight in the past 3 months for any reason other than post-partum weight loss. Participants taking weight loss drugs or using preparations taken for intended weight loss are excluded.
    6. Likely to move away from participating clinics in next 2 years
    7. Current (or anticipated) pregnancy and lactation.
    8. A pregnancy that was completed less than 6 months prior to screening.
    9. Breast feeding within 6 months prior to screening.
    10. Women of childbearing potential who are unwilling to use adequate contraception
    11. Major psychiatric disorder that, in the opinion of clinic staff, would impede the conduct of RISE
  11. Additional conditions may serve as criteria for exclusion at the discretion of the local site.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01779375

Locations
United States, Colorado
Childrens Hospital Colorado Recruiting
Denver, Colorado, United States, 80045
Contact: Rose Moorehead    720-777-2855    Kristen.Nadeau@childrenscolorado.org   
Principal Investigator: Kristen Nadeau, MD         
United States, Connecticut
Yale School of Medicine Pediatric Obesity and Type 2 Diabetes Clinic Recruiting
New Haven, Connecticut, United States, 06511
Contact: Bridget Pierpont, M.A.    203-785-2942    bridget.pierpont@yale.edu   
Principal Investigator: Sonia Caprio, MD         
United States, Indiana
Indiana University Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Tammy Garrett, RN    317-274-7679    tjgarret@iupui.edu   
Principal Investigator: Kieren Mather, MD         
United States, Pennsylvania
Children's Hospital of Pittsburgh of UPMC Recruiting
Pittsburgh, Pennsylvania, United States, 15224
Contact: Kathy Brown    412-692-5846    kathleen.brown@chp.edu   
Principal Investigator: Silva Arslanian, MD         
Sponsors and Collaborators
RISE Study Group
  More Information

No publications provided

Responsible Party: RISE Study Group
ClinicalTrials.gov Identifier: NCT01779375     History of Changes
Other Study ID Numbers: RISE Pediatric, 5U01DK094406-02
Study First Received: January 28, 2013
Last Updated: December 19, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by RISE Study Group:
Children
Pediatric

Additional relevant MeSH terms:
Diabetes Mellitus, Type 2
Glucose Intolerance
Prediabetic State
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Hyperglycemia
Glargine
Insulin
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 22, 2014