RISE Adult Medication Study

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2013 by RISE Study Group
Sponsor:
Collaborator:
Information provided by (Responsible Party):
RISE Study Group
ClinicalTrials.gov Identifier:
NCT01779362
First received: January 28, 2013
Last updated: December 19, 2013
Last verified: May 2013
  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 Intervention Phase
Prediabetes
Type 2 Diabetes
Drug: Metformin
Drug: Liraglutide
Drug: Glargine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Restoring Insulin Secretion Adult Medication Study

Resource links provided by NLM:


Further study details as provided by RISE Study Group:

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.


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.


Other Outcome Measures:
  • Hyperglycemic clamp and OGTT measures of ß-cell Function and Glucose Tolerance [ Time Frame: After 12 months of active treatment ] [ Designated as safety issue: No ]
    Measures derived from the hyperglycemic clamp and the OGTT related to treatment effect at the end of the 12 month active intervention period compared to pre-treatment baseline.


Estimated Enrollment: 255
Study Start Date: April 2013
Estimated Study Completion Date: August 2017
Estimated Primary Completion Date: August 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: Metformin
Other Name: Glucophage
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.
Drug: Metformin
Other Name: Glucophage
Drug: Glargine
Other Name: Insulin glargine, Lantus
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).
Drug: Metformin
Other Name: Glucophage
Drug: Liraglutide
Other Name: Victoza

  Eligibility

Ages Eligible for Study:   20 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01779362

Locations
United States, Illinois
University of Chicago Recruiting
Chicago, Illinois, United States, 60637
Contact: Abby Rue    773-702-4295    arue@medicine.bsd.uchicago.edu   
Principal Investigator: David Ehrmann, MD         
United States, Indiana
Indiana University Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Tammy Garrett, RN    317-274-7679    tjgarret@iupui.edu   
Principal Investigator: Kieren Mather, MD         
United States, Washington
VA Puget Sound Health Care System Recruiting
Seattle, Washington, United States, 98108
Contact: Brenda Mongtomery, RN, MS    206-768-5215    bmont@u.washington.edu   
Principal Investigator: Steven Kahn, MB, ChB         
Sponsors and Collaborators
RISE Study Group
  More Information

No publications provided by RISE Study Group

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: RISE Study Group
ClinicalTrials.gov Identifier: NCT01779362     History of Changes
Other Study ID Numbers: RISE Adult, 5U01DK094406-02
Study First Received: January 28, 2013
Last Updated: December 19, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Diabetes Mellitus, Type 2
Glucose Intolerance
Prediabetic State
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Hyperglycemia
Glargine
Insulin
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 23, 2014