RISE Pediatric Medication Study
Trial Purpose and Description
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.
- 10 Years - 19 Years
- Fasting plasma glucose &ge90 mg/dl plus 2-hour glucose &ge140 mg/dl on 75 gm OGTT plus laboratory-based HbA1c &ge5.8 and &le8.0% if treatment naïve. There is no upper limit for the 2-hour glucose on OGTT. In those taking metformin laboratory-based HbA1c must be &le7.5% if on metformin for <3 months and &le7.0% if on metformin for 3-6 months.
- Age 10-19 years
- Pubertal development Tanner stage >1 as defined by breast stage >1 in girls, and testes >3 cc's in boys.
- Body mass index (BMI) &ge85th percentile but &le50 kg/m2
- Self-reported diabetes <6 months in duration
- Treatment with metformin for <6 months preceding screening
- 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
- An underlying disease that affects glucose metabolism other than type 2 diabetes mellitus
- Taking medications that affect glucose metabolism, or has an underlying condition that is likely to require such medications
- Treatment with insulin for >1 week preceding screening
- Active infections
- Renal disease (serum creatinine >1.2 mg/dl) or serum potassium abnormality (<3.4 or >5.5 mmol/l)
- Anemia (hemoglobin <11 g/dl in girls, <12 g/dl in boys) or known coagulopathy
- 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.
History of conditions that may be precipitated or exacerbated by a study drug:
- Serum alanine transaminase (ALT) more than 3 times the upper limit of normal
- Excessive alcohol intake
- Sub-optimally treated thyroid disease
Conditions or behaviors likely to affect the conduct of the RISE Study
- Participant and/or parents unable or unwilling to give informed consent
- Participant and/or parents unable to adequately communicate with clinic staff
- Another household member is a participant or staff member in RISE
- Current, recent or anticipated participation in another intervention research project that would interfere with any of the interventions/outcomes in RISE
- Weight loss of &ge5% 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.
- Likely to move away from participating clinics in next 2 years
- Current (or anticipated) pregnancy and lactation.
- A pregnancy that was completed less than 6 months prior to screening.
- Breast feeding within 6 months prior to screening.
- Women of childbearing potential who are unwilling to use adequate contraception
- Major psychiatric disorder that, in the opinion of clinic staff, would impede the conduct of RISE
- Additional conditions may serve as criteria for exclusion at the discretion of the local site.
- National Institutes of Health
- Last Updated:
- Study HIC#: