RISE Adult Medication Study (RISE Adult)

April 12, 2023 updated by: RISE Study Group

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

267

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Illinois
      • Chicago, Illinois, United States, 60637
        • University of Chicago
      • Chicago, Illinois, United States, 60612
        • Jesse Brown VA Medical Center
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana University
    • Washington
      • Seattle, Washington, United States, 98108
        • VA Puget Sound Health Care System

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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
Titrated to 1000 mg BID
Other Names:
  • 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
Titrated to 1000 mg BID
Other Names:
  • Glucophage
Drug: Glargine
Titrated to target fasting glucose <90 mg/dl
Other Names:
  • 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.
Drug: Placebo
Matching to metformin 1000 mg BI
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
Titrated to 1000 mg BID
Other Names:
  • Glucophage
Drug: Liraglutide
Titrated to 1.8 mg/day
Other Names:
  • Victoza

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
ß-cell Response Measured by Hyperglycemic Clamp
Time Frame: 3-months after medication washout (Month 15)
Clamp measures of ß-cell response, co-primary outcomes
3-months after medication washout (Month 15)
Insulin Sensitivity, M/I
Time Frame: 3-months after a medication washout
Clamp measure of insulin sensitivity
3-months after a medication washout

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
ACPRg
Time Frame: 3-months after a medication washout
First phase response from the hyperglycemic clamp
3-months after a medication washout
ß-cell Function Measured by Hyperglycemic Clamp Techniques at M12
Time Frame: Secondary analysis was on all participants with a Month 12 visit.
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.

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Hyperglycemic clamp and OGTT measures of ß-cell Function and Glucose Tolerance
Time Frame: After 12 months of active treatment
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.
After 12 months of active treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

RISE Study Group

Collaborators

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2013

Primary Completion (Actual)

February 1, 2019

Study Completion (Actual)

August 1, 2019

Study Registration Dates

First Submitted

January 28, 2013

First Submitted That Met QC Criteria

January 28, 2013

First Posted (Estimate)

January 30, 2013

Study Record Updates

Last Update Posted (Estimate)

May 11, 2023

Last Update Submitted That Met QC Criteria

April 12, 2023

Last Verified

August 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RISE Adult
  • 5U01DK094406-02 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

A de-identified dataset will be made available through the NIDDK repository within 2 years after the final participant visit. Data can be obtained from the NIDDK repository.

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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