This trial is active, not recruiting.

Conditions prediabetes, type 2 diabetes
Treatments metformin, glargine
Phase phase 3
Sponsor RISE Study Group
Collaborator National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Start date April 2013
End date August 2017
Trial size 91 participants
Trial identifier NCT01779375, 5U01DK094406-02, RISE Pediatric


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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
(Active Comparator)
Metformin will be titrated to the maximum dose tolerated (up to 2000 mg/day).
metformin Glucophage
(Active Comparator)
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.
metformin Glucophage
glargine Insulin glargine, Lantus

Primary Outcomes

ß-cell function measured by hyperglycemic clamp techniques
time frame: 3-months after a medication washout

Secondary Outcomes

Hyperglycemic clamp and oral glucose tolerance test (OGTT) measures of ß-cell Function and Glucose Tolerance
time frame: 3-months after a medication washout

Eligibility Criteria

Male or female participants from 10 years up to 19 years old.

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.

Additional Information

Official title Restoring Insulin Secretion Pediatric Medication Study
Trial information was received from ClinicalTrials.gov and was last updated in April 2016.
Information provided to ClinicalTrials.gov by RISE Study Group.