RISE Pediatric Medication Study (RISE Peds)

April 12, 2023 updated by: RISE Study Group

Restoring Insulin Secretion Pediatric Medication Study

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

91

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Colorado
      • Denver, Colorado, United States, 80045
        • Childrens Hospital Colorado
    • Connecticut
      • New Haven, Connecticut, United States, 06511
        • Yale School of Medicine Pediatric Obesity and Type 2 Diabetes Clinic
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana University
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15224
        • Children's Hospital of Pittsburgh of UPMC

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

10 years to 19 years (Child, Adult)

Accepts Healthy Volunteers

Yes

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Metformin alone
Metformin will be titrated to the maximum dose tolerated (up to 2000 mg/day).
Drug: Metformin
Other Names:
  • 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 Names:
  • Glucophage
Drug: Glargine
Other Names:
  • Insulin glargine, Lantus

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
3-months after medication washout (Month 15)
M/I
Time Frame: 3-months after a medication washout
Clamp measure of insulin sensitivity
3-months after a medication washout

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
ACPRg
Time Frame: 3-months after a medication washout
First phase response
3-months after a medication washout
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.
End of active intervention (Month 12).
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.
End of active intervention (Month 12)

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
After 12 months of active treatment, and 3 and 9 months of washout

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

RISE Study Group

Collaborators

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 16, 2013

Primary Completion (Actual)

July 12, 2017

Study Completion (Actual)

April 1, 2018

Study Registration Dates

First Submitted

January 28, 2013

First Submitted That Met QC Criteria

January 28, 2013

First Posted (Estimate)

January 30, 2013

Study Record Updates

Last Update Posted (Actual)

April 14, 2023

Last Update Submitted That Met QC Criteria

April 12, 2023

Last Verified

April 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RISE Pediatric
  • 5U01DK094406-02 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD 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.

IPD Sharing Time Frame

Through the NIDDK repository in 2020, indefinitely.

IPD Sharing Access Criteria

Following NIDDK repository instructions.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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