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Trial record 1 of 1 for:    NCT01779375
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RISE Pediatric Medication Study (RISE Peds)

This study is ongoing, but not recruiting participants.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
RISE Study Group Identifier:
First received: January 28, 2013
Last updated: April 10, 2017
Last verified: April 2017

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
Intervention Model: Parallel Assignment
Masking: None (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 ]
    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 ]
    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 ]
    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.

Enrollment: 91
Study Start Date: April 2013
Estimated Study Completion Date: January 2018
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


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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01779375

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)
  More Information

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: RISE Study Group Identifier: NCT01779375     History of Changes
Other Study ID Numbers: RISE Pediatric
5U01DK094406-02 ( U.S. NIH Grant/Contract )
Study First Received: January 28, 2013
Last Updated: April 10, 2017
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.

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:
Prediabetic State
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Insulin, Globin Zinc
Insulin Glargine
Hypoglycemic Agents
Physiological Effects of Drugs processed this record on September 21, 2017