RISE Adult Medication Study | RxWiki

RISE Adult Medication Study

Overview[ - collapse ][ - ]

Purpose	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.
Condition	Prediabetes Type 2 Diabetes
Intervention	Drug: Metformin Drug: Liraglutide Drug: Glargine
Phase	Phase 3
Sponsor	RISE Study Group
Responsible Party	RISE Study Group
ClinicalTrials.gov Identifier	NCT01779362
First Received	January 28, 2013
Last Updated	December 19, 2013
Last verified	May 2013

Tracking Information[ + expand ][ + ]

First Received Date	January 28, 2013
Last Updated Date	December 19, 2013
Start Date	April 2013
Estimated Primary Completion Date	August 2017
Current Primary Outcome Measures	ß-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 Measures	Hyperglycemic 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 Title	RISE Adult Medication Study
Official Title	Restoring Insulin Secretion Adult Medication Study
Brief 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.
Detailed Description	Not Provided
Study Type	Interventional
Study Phase	Phase 3
Study Design	Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Condition	Prediabetes Type 2 Diabetes
Intervention	Drug: Metformin Other Names: GlucophageDrug: Liraglutide Other Names: VictozaDrug: 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). Participants randomized to the metformin-alone arm will be blinded to treatment. Active Comparator: Glargine followed by Metformin Basal insulin glargine for 3 months titrated to achieve a morning fasting blood glucose of 80-90 mg/dl, followed by open-label metformin (titrated up to 2000 mg/day) for 9 months. Placebo Comparator: Placebo Placebo - masked to metformin-alone. Placebo will be titrated to the maximum number of tablets equivalent to maximum dose of metformin. Active Comparator: Liraglutide + Metformin Liraglutide + open-label Metformin. Liraglutide will be titrated to the maximum dose tolerated (up to 1.8 mg/day) after which metformin will be titrated to the maximum dose tolerated (up to 2000 mg/day).

Recruitment Information[ + expand ][ + ]

Recruitment Status	Recruiting
Estimated Enrollment	255
Estimated Completion Date	August 2017
Estimated Primary Completion Date	August 2017
Eligibility Criteria	Inclusion Criteria: 1. Fasting plasma glucose 95-125 mg/dl plus 2-hour glucose ≥140 mg/dl on 75 gm OGTT plus HbA1c ≥5.8 and ≤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 ≤40 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.
Gender	Both
Ages	20 Years
Accepts Healthy Volunteers	Accepts Healthy Volunteers
Contacts	Not Provided
Location Countries	United States

Administrative Information[ + expand ][ + ]

NCT Number	NCT01779362
Other Study ID Numbers	RISE Adult
Has Data Monitoring Committee	Yes
Information Provided By	RISE Study Group
Study Sponsor	RISE Study Group
Collaborators	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators	Not Provided
Verification Date	May 2013

Locations[ + expand ][ + ]

University of Chicago	Chicago, Illinois, United States, 60637 Contact: Abby Rue \| 773-702-4295 \| arue@medicine.bsd.uchicago.edu Principal Investigator: David Ehrmann, 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
VA Puget Sound Health Care System	Seattle, Washington, United States, 98108 Contact: Brenda Mongtomery, RN, MS \| 206-768-5215 \| bmont@u.washington.edu Principal Investigator: Steven Kahn, MB, ChB Recruiting