RISE Pediatric Medication Study

Overview[ - collapse ][ - ]

Purpose 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.
ConditionPrediabetes
Type 2 Diabetes
InterventionDrug: Metformin
Drug: Glargine
PhasePhase 3
SponsorRISE Study Group
Responsible PartyRISE Study Group
ClinicalTrials.gov IdentifierNCT01779375
First ReceivedJanuary 28, 2013
Last UpdatedDecember 19, 2013
Last verifiedDecember 2013

Tracking Information[ + expand ][ + ]

First Received DateJanuary 28, 2013
Last Updated DateDecember 19, 2013
Start DateApril 2013
Estimated Primary Completion DateAugust 2017
Current Primary Outcome Measuresß-cell function measured by hyperglycemic clamp techniques [Time Frame: 3-months after a medication washout] [Designated as safety issue: No]Participants will have 12-months of active therapy and 3-months of washout after which the primary outcome will be assessed.
Current Secondary Outcome MeasuresHyperglycemic clamp and oral glucose tolerance test (OGTT) measures of ß-cell Function and Glucose Tolerance [Time Frame: 3-months after a medication washout] [Designated as safety issue: No]Measures derived from the hyperglycemic clamp that are not specified as primary outcomes and measures derived from the OGTT.

Descriptive Information[ + expand ][ + ]

Brief TitleRISE Pediatric Medication Study
Official TitleRestoring 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 DescriptionNot Provided
Study TypeInterventional
Study PhasePhase 3
Study DesignAllocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Condition
  • Prediabetes
  • Type 2 Diabetes
InterventionDrug: Metformin
Other Names:
GlucophageDrug: Glargine
Other Names:
Insulin glargine, Lantus
Study Arm (s)
  • Active Comparator: Metformin alone
    Metformin will be titrated to the maximum dose tolerated (up to 2000 mg/day).
  • 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.

Recruitment Information[ + expand ][ + ]

Recruitment StatusRecruiting
Estimated Enrollment90
Estimated Completion DateAugust 2017
Estimated Primary Completion DateAugust 2017
Eligibility Criteria
Inclusion Criteria:

1. Fasting plasma glucose ≥90 mg/dl plus 2-hour glucose ≥140 mg/dl on 75 gm OGTT plus
laboratory-based HbA1c ≥5.8 and ≤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.
GenderBoth
Ages10 Years
Accepts Healthy VolunteersAccepts Healthy Volunteers
ContactsNot Provided
Location CountriesUnited States

Administrative Information[ + expand ][ + ]

NCT Number NCT01779375
Other Study ID NumbersRISE Pediatric
Has Data Monitoring CommitteeYes
Information Provided ByRISE Study Group
Study SponsorRISE Study Group
CollaboratorsNational Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators Not Provided
Verification DateDecember 2013

Locations[ + expand ][ + ]

Childrens Hospital Colorado
Denver, Colorado, United States, 80045
Contact: Rose Moorehead | 720-777-2855 | Kristen.Nadeau@childrenscolorado.org
Principal Investigator: Kristen Nadeau, MD
Recruiting
Yale School of Medicine Pediatric Obesity and Type 2 Diabetes Clinic
New Haven, Connecticut, United States, 06511
Contact: Bridget Pierpont, M.A. | 203-785-2942 | bridget.pierpont@yale.edu
Principal Investigator: Sonia Caprio, MD
Recruiting
Indiana University
Indianapolis, Indiana, United States, 46202
Contact: Tammy Garrett, RN | 317-274-7679 | tjgarret@iupui.edu
Principal Investigator: Kieren Mather, MD
Recruiting
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, United States, 15224
Contact: Kathy Brown | 412-692-5846 | kathleen.brown@chp.edu
Principal Investigator: Silva Arslanian, MD
Recruiting