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RISE Pediatric Medication Study (RISE Peds)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. 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

Tracking Information
First Submitted Date  ICMJE January 28, 2013
First Posted Date  ICMJE January 30, 2013
Results First Submitted Date  ICMJE August 30, 2018
Results First Posted Date  ICMJE October 9, 2018
Last Update Posted Date December 10, 2019
Actual Study Start Date  ICMJE June 16, 2013
Actual Primary Completion Date July 12, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 1, 2018)
  • 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
  • M/I [ Time Frame: 3-months after a medication washout ]
    Clamp measure of insulin sensitivity
Original Primary Outcome Measures  ICMJE
 (submitted: January 28, 2013)
ß-cell function measured by hyperglycemic clamp techniques [ Time Frame: 3-months after a medication washout ]
Participants will have 12-months of active therapy and 3-months of washout after which the primary outcome will be assessed.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 1, 2018)
  • ACPRg [ Time Frame: 3-months after a medication washout ]
    First phase response
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 28, 2013)
Hyperglycemic clamp and oral glucose tolerance test (OGTT) measures of ß-cell Function and Glucose Tolerance [ Time Frame: 3-months after a medication washout ]
Measures derived from the hyperglycemic clamp that are not specified as primary outcomes and measures derived from the OGTT.
Current Other Pre-specified Outcome Measures
 (submitted: October 1, 2018)
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.
Original Other Pre-specified Outcome Measures
 (submitted: January 28, 2013)
Hyperglycemic clamp and OGTT measures of ß-cell Function and Glucose Tolerance [ Time Frame: After 12 months of active treatment ]
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.
Descriptive Information
Brief Title  ICMJE RISE Pediatric Medication Study
Official Title  ICMJE Restoring Insulin Secretion Pediatric Medication Study
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Prediabetes
  • Type 2 Diabetes
Intervention  ICMJE
  • Drug: Metformin
    Other Name: Glucophage
  • Drug: Glargine
    Other Name: Insulin glargine, Lantus
Study Arms  ICMJE
  • Active Comparator: Metformin alone
    Metformin will be titrated to the maximum dose tolerated (up to 2000 mg/day).
    Intervention: Drug: Metformin
  • 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
    • Drug: Glargine
Publications *

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 4, 2016)
Original Estimated Enrollment  ICMJE
 (submitted: January 28, 2013)
Actual Study Completion Date  ICMJE April 2018
Actual Primary Completion Date July 12, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 10 Years to 19 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT01779375
Other Study ID Numbers  ICMJE RISE Pediatric
5U01DK094406-02 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
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
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Time Frame: Through the NIDDK repository in 2020, indefinitely.
Access Criteria: Following NIDDK repository instructions.
Responsible Party RISE Study Group
Study Sponsor  ICMJE RISE Study Group
Collaborators  ICMJE National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators  ICMJE Not Provided
PRS Account RISE Study Group
Verification Date November 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP