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RISE Pediatric Medication Study (RISE Peds)

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ClinicalTrials.gov Identifier: NCT01779375
Recruitment Status : Completed
First Posted : January 30, 2013
Results First Posted : October 9, 2018
Last Update Posted : December 10, 2019
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
RISE Study Group

Brief Summary:

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 or disease Intervention/treatment Phase
Prediabetes Type 2 Diabetes Drug: Metformin Drug: Glargine Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 91 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Restoring Insulin Secretion Pediatric Medication Study
Actual Study Start Date : June 16, 2013
Actual Primary Completion Date : July 12, 2017
Actual Study Completion Date : April 2018

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
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

Primary Outcome Measures :
  1. ß-cell Response Measured by Hyperglycemic Clamp [ Time Frame: 3-months after medication washout (Month 15) ]
    Clamp measures of ß-cell response, co-primary outcomes

  2. M/I [ Time Frame: 3-months after a medication washout ]
    Clamp measure of insulin sensitivity

Secondary Outcome Measures :
  1. ACPRg [ Time Frame: 3-months after a medication washout ]
    First phase response

  2. ß-cell Function Measured by Hyperglycemic Clamp Techniques at M12 [ Time Frame: End of active intervention (Month 12). ]
    Participants had 12-months of active therapy. Secondary results at the end of active intervention.

  3. Clamp Measure of Insulin Sensitivity [ Time Frame: End of active intervention (Month 12) ]
    Participants had 12-months of active therapy. Secondary results at the end of active intervention.

Other Outcome Measures:
  1. OGTT Measures of ß-cell Function and Glucose Tolerance [ Time Frame: After 12 months of active treatment, and 3 and 9 months of washout ]
    Measures derived the OGTT at the end of the 12 month active intervention period, and following a 3-month and 9-month washout.

Information from the National Library of Medicine

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Ages Eligible for Study:   10 Years to 19 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

  1. Fasting plasma glucose ≥90 mg/dl plus 2-hour glucose ≥140 mg/dl on 75 gm OGTT plus laboratory-based HbA1c ≤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.

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): NCT01779375

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United States, Colorado
Childrens Hospital Colorado
Denver, Colorado, United States, 80045
United States, Connecticut
Yale School of Medicine Pediatric Obesity and Type 2 Diabetes Clinic
New Haven, Connecticut, United States, 06511
United States, Indiana
Indiana University
Indianapolis, Indiana, United States, 46202
United States, Pennsylvania
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, United States, 15224
Sponsors and Collaborators
RISE Study Group
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
  Study Documents (Full-Text)

Documents provided by RISE Study Group:
Study Protocol  [PDF] May 1, 2016
Informed Consent Form  [PDF] May 21, 2013
Statistical Analysis Plan  [PDF] November 1, 2017

Publications of Results:
Other Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: RISE Study Group
ClinicalTrials.gov Identifier: NCT01779375    
Other Study ID Numbers: RISE Pediatric
5U01DK094406-02 ( U.S. NIH Grant/Contract )
First Posted: January 30, 2013    Key Record Dates
Results First Posted: October 9, 2018
Last Update Posted: December 10, 2019
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Will share all research data via the NIDDK repository 2 years after final patient visit from the RISE consortium in ~2020. Data may be obtained from the repository directly.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Time Frame: Through the NIDDK repository in 2020, indefinitely.
Access Criteria: Following NIDDK repository instructions.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by RISE Study Group:
Additional relevant MeSH terms:
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Prediabetic State
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Insulin Glargine
Hypoglycemic Agents
Physiological Effects of Drugs