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RISE Adult Medication Study

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2014 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: November 5, 2014
Last verified: November 2014

January 28, 2013
November 5, 2014
April 2013
August 2017   (final data collection date for primary outcome measure)
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.
Same as current
Complete list of historical versions of study NCT01779362 on ClinicalTrials.gov Archive Site
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.
Same as current
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.
Same as current
 
RISE Adult Medication Study
Restoring Insulin Secretion Adult Medication Study

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.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • Prediabetes
  • Type 2 Diabetes
  • Drug: Metformin
    Other Name: Glucophage
  • Drug: Liraglutide
    Other Name: Victoza
  • Drug: Glargine
    Other Name: Insulin glargine, Lantus
  • 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.
    Intervention: Drug: Metformin
  • 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.
    Interventions:
    • Drug: Metformin
    • Drug: Glargine
  • 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).
    Interventions:
    • Drug: Metformin
    • Drug: Liraglutide
RISE Consortium. Restoring Insulin Secretion (RISE): design of studies of β-cell preservation in prediabetes and early type 2 diabetes across the life span. Diabetes Care. 2014 Mar;37(3):780-8. doi: 10.2337/dc13-1879. Epub 2013 Nov 5.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
255
August 2017
August 2017   (final data collection date for primary outcome measure)

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.
Both
20 Years to 65 Years
Yes
United States
 
NCT01779362
RISE Adult, 5U01DK094406-02
Yes
RISE Study Group
RISE Study Group
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Not Provided
RISE Study Group
November 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP