RISE Adult Medication Study (RISE Adult)
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| ClinicalTrials.gov Identifier: NCT01779362 |
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Recruitment Status :
Completed
First Posted : January 30, 2013
Results First Posted : May 11, 2023
Last Update Posted : May 11, 2023
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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 or disease | Intervention/treatment | Phase |
|---|---|---|
| Prediabetes Type 2 Diabetes | Drug: Metformin Drug: Liraglutide Drug: Glargine Drug: Placebo | Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 267 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | Restoring Insulin Secretion Adult Medication Study |
| Study Start Date : | April 2013 |
| Actual Primary Completion Date : | February 2019 |
| Actual Study Completion Date : | August 2019 |
| Arm | Intervention/treatment |
|---|---|
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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.
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Drug: Metformin
Titrated to 1000 mg BID
Other Name: Glucophage |
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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.
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Drug: Metformin
Titrated to 1000 mg BID
Other Name: Glucophage Drug: Glargine Titrated to target fasting glucose <90 mg/dl
Other Name: Insulin glargine, Lantus |
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Placebo Comparator: Placebo
Placebo - masked to metformin-alone. Placebo will be titrated to the maximum number of tablets equivalent to maximum dose of metformin.
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Drug: Placebo
Matching to metformin 1000 mg BI |
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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).
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Drug: Metformin
Titrated to 1000 mg BID
Other Name: Glucophage Drug: Liraglutide Titrated to 1.8 mg/day
Other Name: Victoza |
- 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
- Insulin Sensitivity, M/I [ Time Frame: 3-months after a medication washout ]Clamp measure of insulin sensitivity
- ACPRg [ Time Frame: 3-months after a medication washout ]First phase response from the hyperglycemic clamp
- 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.
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| Ages Eligible for Study: | 20 Years to 65 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | Yes |
Inclusion Criteria:
- 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.
- Age 20-65 years
- Body mass index (BMI) ≥25 kg/m2 but ≤50 kg/m2
- Self-reported diabetes <1 year in duration
- Drug naïve (no prior to oral glucose lowering agent(s), insulin or other injectable glucose lowering agents)
Exclusion Criteria:
- 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
- An underlying disease that affects glucose metabolism other than type 2 diabetes
- Taking medications that affect glucose metabolism, or has an underlying condition that is likely to require such medications
- Active infections
- 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)
- Anemia (hemoglobin <11 g/dl in women, <12 g/dl in men) or known coagulopathy
- Cardiovascular disease, including uncontrolled hypertension. Participants must be able to safely tolerate administration of intravenous fluids required during clamp studies.
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History of conditions that may be precipitated or exacerbated by a study drug:
- Pancreatitis
- Serum alanine transaminase (ALT) more than 3 times the upper limit of normal
- Excessive alcohol intake
- Suboptimally treated thyroid disease
- Medullary carcinoma of the thyroid or MEN-2 (in participant or a family history)
- Hypertriglyceridemia (>400 mg/dl despite treatment)
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Conditions or behaviors likely to affect the conduct of the RISE Study
- Unable or unwilling to give informed consent
- Unable to adequately communicate with clinic staff
- Another household member is a participant or staff member in RISE
- Current, recent or anticipated participation in another intervention research project that would interfere with any of the interventions/outcomes in RISE
- 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.
- Likely to move away from participating clinics in next two years
- Women of childbearing potential who are unwilling to use adequate contraception
- Current (or anticipated) pregnancy and lactation.
- Major psychiatric disorder that, in the opinion of clinic staff, would impede the conduct of RISE
- Additional conditions may serve as criteria for exclusion at the discretion of the local site.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01779362
| United States, Illinois | |
| Jesse Brown VA Medical Center | |
| Chicago, Illinois, United States, 60612 | |
| University of Chicago | |
| Chicago, Illinois, United States, 60637 | |
| United States, Indiana | |
| Indiana University | |
| Indianapolis, Indiana, United States, 46202 | |
| United States, Washington | |
| VA Puget Sound Health Care System | |
| Seattle, Washington, United States, 98108 | |
Documents provided by RISE Study Group:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | RISE Study Group |
| ClinicalTrials.gov Identifier: | NCT01779362 |
| Other Study ID Numbers: |
RISE Adult 5U01DK094406-02 ( U.S. NIH Grant/Contract ) |
| First Posted: | January 30, 2013 Key Record Dates |
| Results First Posted: | May 11, 2023 |
| Last Update Posted: | May 11, 2023 |
| Last Verified: | August 2018 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| 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. |
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Prediabetic State Diabetes Mellitus Glucose Metabolism Disorders Metabolic Diseases Endocrine System Diseases Metformin Insulin Glargine |
Liraglutide Hypoglycemic Agents Physiological Effects of Drugs Incretins Hormones Hormones, Hormone Substitutes, and Hormone Antagonists |