RISE Pediatric Medication Study

Type 2 Diabetes Clinical Trial

— RISE Peds  

Official title:

Restoring Insulin Secretion Pediatric Medication Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01779375
• Other study ID #: RISE Pediatric
• Secondary ID: 5U01DK094406-02
• Status: Completed
• Phase: Phase 3
• Start date: June 16, 2013
• Est. completion date: April 2018

Study information

• Verified date: April 2023
• Source: RISE Study Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 91
• Est. completion date: April 2018
• Est. primary completion date: July 12, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 10 Years to 19 Years

Eligibility

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.

Related Conditions & MeSH terms

• Prediabetes
• Prediabetic State
• Type 2 Diabetes

Intervention

Drug:
• Metformin

• Glargine

Locations

Country	Name	City	State
United States	Childrens Hospital Colorado	Denver	Colorado
United States	Indiana University	Indianapolis	Indiana
United States	Yale School of Medicine Pediatric Obesity and Type 2 Diabetes Clinic	New Haven	Connecticut
United States	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
RISE Study Group	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

References & Publications (5)

Hannon TS, Kahn SE, Utzschneider KM, Buchanan TA, Nadeau KJ, Zeitler PS, Ehrmann DA, Arslanian SA, Caprio S, Edelstein SL, Savage PJ, Mather KJ; RISE Consortium. Review of methods for measuring beta-cell function: Design considerations from the Restoring Insulin Secretion (RISE) Consortium. Diabetes Obes Metab. 2018 Jan;20(1):14-24. doi: 10.1111/dom.13005. Epub 2017 Jun 22. — View Citation

RISE Consortium. Impact of Insulin and Metformin Versus Metformin Alone on beta-Cell Function in Youth With Impaired Glucose Tolerance or Recently Diagnosed Type 2 Diabetes. Diabetes Care. 2018 Aug;41(8):1717-1725. doi: 10.2337/dc18-0787. Epub 2018 Jun 25 — View Citation

RISE Consortium. Metabolic Contrasts Between Youth and Adults With Impaired Glucose Tolerance or Recently Diagnosed Type 2 Diabetes: I. Observations Using the Hyperglycemic Clamp. Diabetes Care. 2018 Aug;41(8):1696-1706. doi: 10.2337/dc18-0244. Epub 2018 Jun 25. — View Citation

RISE Consortium. Metabolic Contrasts Between Youth and Adults With Impaired Glucose Tolerance or Recently Diagnosed Type 2 Diabetes: II. Observations Using the Oral Glucose Tolerance Test. Diabetes Care. 2018 Aug;41(8):1707-1716. doi: 10.2337/dc18-0243. Epub 2018 Jun 25. — View Citation

RISE Consortium. Restoring Insulin Secretion (RISE): design of studies of beta-cell preservation in prediabetes and early type 2 diabetes across the life span. Diabetes Care. 2014;37(3):780-8. doi: 10.2337/dc13-1879. Epub 2013 Nov 5. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	OGTT Measures of ß-cell Function and Glucose Tolerance	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
Primary	ß-cell Response Measured by Hyperglycemic Clamp	Clamp measures of ß-cell response, co-primary outcomes	3-months after medication washout (Month 15)
Primary	M/I	Clamp measure of insulin sensitivity	3-months after a medication washout
Secondary	ACPRg	First phase response	3-months after a medication washout
Secondary	ß-cell Function Measured by Hyperglycemic Clamp Techniques at M12	Participants had 12-months of active therapy. Secondary results at the end of active intervention.	End of active intervention (Month 12).
Secondary	Clamp Measure of Insulin Sensitivity	Participants had 12-months of active therapy. Secondary results at the end of active intervention.	End of active intervention (Month 12)