RISE Adult Medication Study

Type 2 Diabetes Clinical Trial

— RISE Adult  

Official title:

Restoring Insulin Secretion Adult Medication Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01779362
• Other study ID #: RISE Adult
• Secondary ID: 5U01DK094406-02
• Status: Completed
• Phase: Phase 3
• Start date: April 2013
• Est. completion date: August 2019

Study information

• Verified date: August 2018
• Source: RISE Study Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The RISE Adult Medication Study is a 4-arm, 3-center, clinical trial of adults 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. Adult participants (ages 20-65) will be randomized to one of the following treatment regimens: (1) blinded placebo, (2) blinded metformin alone, (3) early intensive insulin treatment with basal insulin glargine followed by open-label metformin, (4) the glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide plus open-label 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: 267
• Est. completion date: August 2019
• Est. primary completion date: February 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 20 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Fasting plasma glucose 95-125 mg/dl plus 2-hour glucose =140 mg/dl on 75 gm OGTT plus HbA1c =7.0%. There is no upper limit for the 2-hour glucose on OGTT.

2. Age 20-65 years

3. Body mass index (BMI) =25 kg/m2 but =50 kg/m2

4. Self-reported diabetes <1 year in duration

5. Drug naïve (no prior to oral glucose lowering agent(s), insulin or other injectable glucose lowering agents)

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

3. Taking medications that affect glucose metabolism, or has an underlying condition that is likely to require such medications

4. Active infections

5. Renal disease (serum creatinine >1.4 mg/dl for men; >1.3 mg/dl for women) or serum potassium abnormality (<3.4 or >5.5 mmol/l)

6. Anemia (hemoglobin <11 g/dl in women, <12 g/dl in men) or known coagulopathy

7. Cardiovascular disease, including uncontrolled hypertension. Participants must be able to safely tolerate administration of intravenous fluids required during clamp studies.

8. History of conditions that may be precipitated or exacerbated by a study drug:

1. Pancreatitis

2. Serum alanine transaminase (ALT) more than 3 times the upper limit of normal

3. Excessive alcohol intake

4. Suboptimally treated thyroid disease

5. Medullary carcinoma of the thyroid or MEN-2 (in participant or a family history)

6. Hypertriglyceridemia (>400 mg/dl despite treatment)

9. Conditions or behaviors likely to affect the conduct of the RISE Study

1. Unable or unwilling to give informed consent

2. 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% in past three 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 two years

7. Women of childbearing potential who are unwilling to use adequate contraception

8. Current (or anticipated) pregnancy and lactation.

9. Major psychiatric disorder that, in the opinion of clinic staff, would impede the conduct of RISE

10. 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
Titrated to 1000 mg BID
• Liraglutide
Titrated to 1.8 mg/day
• Glargine
Titrated to target fasting glucose <90 mg/dl
• Placebo
Matching to metformin 1000 mg BI

Locations

Country	Name	City	State
United States	Jesse Brown VA Medical Center	Chicago	Illinois
United States	University of Chicago	Chicago	Illinois
United States	Indiana University	Indianapolis	Indiana
United States	VA Puget Sound Health Care System	Seattle	Washington

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 (2)

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. 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
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	Insulin Sensitivity, M/I	Clamp measure of insulin sensitivity	3-months after a medication washout
Secondary	ACPRg	First phase response from the hyperglycemic clamp	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.	Secondary analysis was on all participants with a Month 12 visit.