Back to resultsEffect of Subcutaneous Semaglutide on Kidney Transplant Candidacy (RAISE-KT)
Primary Purpose
CKD, Diabetic Kidney Disease, Type 2 Diabetes Mellitus in Obese
Status
Terminated
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Semaglutide 2 mg/1.5 ml (1.34 mg/ml), prefilled pen-injector for subcutaneous injection solution
Placebo 1.5 ml, prefilled pen-injector for subcutaneous injection solution
Sponsored by
About this trial
This is an interventional treatment trial for CKD focused on measuring ckd, obesity, kidney transplant, transplant wait list, diabetic kidney disease, glp-1, semaglutide
Eligibility Criteria
Inclusion Criteria:
- - Age ≥ 18 years
- - BMI 25-45 kg/m2
- - T2DM
- - Advanced CKD* (last eGFR <30 ml/min/1.73m2 in EHR or ESKD on dialysis prior to screening) or stage G3B/A2-3 CKD (eGFR 30 to <45 ml/min/1.73m2 with albumin/creatinine ratio >30 mg/g).
- - Fulfill kidney transplant listing criteria except for one or more of the following reasons (1: uncontrolled diabetes [A1c ≥9%); 2: severe obesity (BMI ≥ 40 kg/m2 or BMI 35-40 kg/m2 with waist circumference >120 cm). See exclusion criteria for general contraindications used for transplant listing used by majority of U.S. transplant centers].
- - Ability to provide informed consent before any trial-related activities
- Access to a telephone
- The cause of the CKD does not need to be due specifically to diabetes
Exclusion Criteria (General contraindications used for transplant listing used by majority of U.S. transplant centers)
- - Active malignancy
- - History of pancreatitis
- - Active substance abuse
- - Severe COPD
- - Pulmonary fibrosis
- - Symptomatic angina or recent myocardial infarction within 6 months
- - Severe peripheral vascular disease
- - Cirrhosis
- - New York Health Association (NYHA) Class III-IV congestive heart failure
- - Severe cognitive impairment
- - Drug addiction
- - History of non-adherence to therapy
- - Active infection
- Expected life expectancy < 5 years
Additional exclusion criteria
- - Type 1 diabetes mellitus
- - History of diabetic ketoacidosis within the last 12 months
- - Planning on undergoing bariatric surgery in next 9 months.
- - Pregnant, breast-feeding, or planned pregnancy prior to the end of participation or not using adequate contraceptive measures
- - Self-reported average consumption of > 21 alcoholic beverages per week or binge drinking
- - Psychiatric hospitalization in past year
- - Principal investigator discretion (i.e. concerns about safety, compliance)
- - Known or suspected allergy to trial medication
- - Previous participation (i.e. randomized) in this trial
- - Use of GLP1-RA or pramlintide within 90 days prior to screening
- - Use of metformin (contraindicated with eGFR < 30 ml/min/1.73m2)
- - Use of DPP-4 inhibitors within 30 days prior to screening
- - Personal or family history of medullary thyroid cancer, multiple endocrine neoplasia types 2A and 2B syndrome
- - Last hemoglobin A1c ≥ 12% or A1c <6% (to avoid risk of hypoglycemia) prior to screening
Sites / Locations
- Geisinger Medical Center
- Geisinger Wyoming Valley
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Semaglutide
Placebo
Arm Description
This arm will receive semaglutide.
This arm will receive placebo.
Outcomes
Primary Outcome Measures
Kidney transplant eligibility
Proportion either listed for kidney transplant at 9 months or meeting the following kidney transplant candidacy criteria for A1c (<9%) and obesity (BMI <35 kg/m2 or BMI 35-40 kg/m2 with waist circumference <120 cm)
Secondary Outcome Measures
Change in hemoglobin A1c (HgbA1c)
HgbA1c will be collected using routine procedures and measured on the same day at the central Geisinger laboratory by Turbidimetric inhibition immunoassay.
Change in BMI
Weight will be measured at each study visit in light clothing without shoes by trained, certified staff using a calibrated, digital scale. Scales will be calibrated annually. Height will be measured at the initial study visit to the nearest 0.1 cm using a calibrated, wall-mounted stadiometer without shoes on a firm, level surface, with head in the horizontal plane.
Change in waist circumference
Waist circumference will be measured at each study visit to the nearest 0.1 cm using a Gulick II tape measure.
Change in waist-to-hip ratio
Hip circumference will also be measured to the nearest 0.1 cm using a Gulick II tape measure, and waist-to-hip ratio will be calculated.
Change in body fat percentage
Measured using bioelectrical impedance analysis
Activation on the transplant list
Assessed by Geisinger kidney transplant committee (blinded to randomization assignment, independent of investigators)
Receipt of kidney transplant
Confirmed by review of electronic health record (EHR)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04741074
Brief Title
Effect of Subcutaneous Semaglutide on Kidney Transplant Candidacy
Acronym
RAISE-KT
Official Title
A RAndomized trIal Examining the Effect of Subcutaneous Semaglutide on Kidney Transplant Candidacy for Patients With Stage 4-5 CKD or Dialysis-dependent ESKD
Study Type
Interventional
2. Study Status
Record Verification Date
February 2023
Overall Recruitment Status
Terminated
Why Stopped
low recruitment
Study Start Date
July 23, 2021 (Actual)
Primary Completion Date
January 31, 2023 (Actual)
Study Completion Date
January 31, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Geisinger Clinic
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This randomized study evaluates the effect of subcutaneous semaglutide /in combination with lifestyle counseling in patients with type 2 diabetes mellitus (T2DM), overweight/obesity, and stage 4-5 chronic kidney disease (CKD) or dialysis-dependent end-stage kidney disease (ESKD) on patients' eligibility for kidney transplantation at the end of 9 months.
Detailed Description
Transplant policies regarding listing consider uncontrolled diabetes and severe obesity to be contraindications though there is great variability for exact BMI (35-45 kg/m2) and A1c (9-10%) thresholds for listing by center. Glucagon-lowering peptide-1 receptor agonists (GLP-1 RAs) offer great promise in this population as they have been shown to reduce weight, central adiposity, A1c, and risk of cardiovascular outcomes with similar effects in patients with and without CKD.
In this double-blind, placebo-controlled randomized controlled trial, the investigators will evaluate the effect of subcutaneous semaglutide 1.34 mg/ml (up to 1.0 mg per week) in combination with lifestyle counseling in patients with T2DM, overweight/obesity, and stage 4-5 CKD or dialysis-dependent ESKD on patients' eligibility for kidney transplantation in terms of diabetes control (A1c <9%) and obesity (BMI <35 kg/m2 or 35-40 kg/m2 with waist circumference <120 cm) at the end of 9 months.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
CKD, Diabetic Kidney Disease, Type 2 Diabetes Mellitus in Obese, Obesity, Severe Obesity
Keywords
ckd, obesity, kidney transplant, transplant wait list, diabetic kidney disease, glp-1, semaglutide
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
This is a placebo-controlled double-blind clinical trial. Study investigators and participants will be blinded to treatment allocation.
Allocation
Randomized
Enrollment
15 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Semaglutide
Arm Type
Active Comparator
Arm Description
This arm will receive semaglutide.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
This arm will receive placebo.
Intervention Type
Drug
Intervention Name(s)
Semaglutide 2 mg/1.5 ml (1.34 mg/ml), prefilled pen-injector for subcutaneous injection solution
Other Intervention Name(s)
semaglutide
Intervention Description
Dose will be started at 0.25 mg per week. Dose escalation will occur every 4 weeks to mitigate risk of gastrointestinal side effects to a maximum dose of 1.0 mg per week.
Intervention Type
Drug
Intervention Name(s)
Placebo 1.5 ml, prefilled pen-injector for subcutaneous injection solution
Other Intervention Name(s)
placebo
Intervention Description
Matched placebo solution for injection will be provided by Novo Nordisk in a 1.5 ml pre-filled pen-injector for subcutaneous injection with the same instructions on dose escalation.
Primary Outcome Measure Information:
Title
Kidney transplant eligibility
Description
Proportion either listed for kidney transplant at 9 months or meeting the following kidney transplant candidacy criteria for A1c (<9%) and obesity (BMI <35 kg/m2 or BMI 35-40 kg/m2 with waist circumference <120 cm)
Time Frame
Ascertained at the end of 9 months
Secondary Outcome Measure Information:
Title
Change in hemoglobin A1c (HgbA1c)
Description
HgbA1c will be collected using routine procedures and measured on the same day at the central Geisinger laboratory by Turbidimetric inhibition immunoassay.
Time Frame
From baseline to 9 months
Title
Change in BMI
Description
Weight will be measured at each study visit in light clothing without shoes by trained, certified staff using a calibrated, digital scale. Scales will be calibrated annually. Height will be measured at the initial study visit to the nearest 0.1 cm using a calibrated, wall-mounted stadiometer without shoes on a firm, level surface, with head in the horizontal plane.
Time Frame
From baseline to 9 months
Title
Change in waist circumference
Description
Waist circumference will be measured at each study visit to the nearest 0.1 cm using a Gulick II tape measure.
Time Frame
From baseline to 9 months
Title
Change in waist-to-hip ratio
Description
Hip circumference will also be measured to the nearest 0.1 cm using a Gulick II tape measure, and waist-to-hip ratio will be calculated.
Time Frame
From baseline to 9 months
Title
Change in body fat percentage
Description
Measured using bioelectrical impedance analysis
Time Frame
From baseline to 9 months
Title
Activation on the transplant list
Description
Assessed by Geisinger kidney transplant committee (blinded to randomization assignment, independent of investigators)
Time Frame
Assessed at end of 9 months
Title
Receipt of kidney transplant
Description
Confirmed by review of electronic health record (EHR)
Time Frame
Assessed at end of 9 months
Other Pre-specified Outcome Measures:
Title
Change in Low-Density Lipoprotein (LDL)
Description
Collected at a Geisinger lab using routine procedures and measured on the same day at the central Geisinger laboratory by spectrophotometry.
Time Frame
Baseline to 9 months
Title
Change in triglycerides
Description
Collected at a Geisinger lab using routine procedures and measured on the same day at the central Geisinger laboratory by spectrophotometry.
Time Frame
Baseline to 9 months
Title
Change in systolic blood pressure
Description
Automated office blood pressure (AOBP) will be measured (attended) using the OMRON 907-XL machine, with a 5-minute rest period in the seated position, followed by 3 measurements separated by 1-minute time intervals by trained research staff. Mid-arm circumference will be measured, and a cuff of appropriate size will be identified and the same size cuff will used for both visits.
Time Frame
Baseline to 9 months
Title
Change in diastolic blood pressure
Description
Automated office blood pressure (AOBP) will be measured (attended) using the OMRON 907-XL machine, with a 5-minute rest period in the seated position, followed by 3 measurements separated by 1-minute time intervals by trained research staff. Mid-arm circumference will be measured, and a cuff of appropriate size will be identified and the same size cuff will used for both visits.
Time Frame
Baseline to 9 months
Title
Change in albuminuria among subset of participants without end-stage kidney disease
Description
Testing at the central Geisinger laboratory, using immunoturbidimetry (albumin) and Jaffe/Enzymatic (Urine Creatinine)
Time Frame
Baseline to 9 months
Title
Change in estimated glomerular filtration (eGFR) rate among subset of participants without end-stage kidney disease
Description
Testing at central Geisinger lab; Creatinine-based CKD-EPI equation
Time Frame
Baseline to 9 months
Title
All-cause hospitalizations
Description
Collected using Geisinger EHR data
Time Frame
Entire 9-month study period
Title
Cardiovascular disease (CVD) events
Description
Collected using Geisinger EHR data using ICD codes for CVD-related hospitalizations
Time Frame
Entire 9-month study period
Title
Proportion experiencing doubling of creatinine or end-stage kidney disease
Description
Collected using Geisinger EHR data using ICD codes
Time Frame
Entire 9-month study period
Title
Proportion experiencing death
Description
Collected using Geisinger EHR data
Time Frame
Entire 9-month study period
Title
Proportion experiencing gastrointestinal disorders
Description
Assessed at each study visit
Time Frame
Entire 9-month study period
Title
Proportion experiencing gallbladder disorders
Description
Assessed at each study visit
Time Frame
Entire 9-month study period
Title
Proportion experiencing neoplasms
Description
Assessed at each study visit
Time Frame
Entire 9-month study period
Title
Proportion experiencing hepatic events
Description
Assessed at each study visit
Time Frame
Entire 9-month study period
Title
Proportion experiencing allergic reactions
Description
Assessed at each study visit
Time Frame
Entire 9-month study period
Title
Proportion experiencing injection-site reactions
Description
Assessed at each study visit
Time Frame
Entire 9-month study period
Title
Proportion experiencing hypoglycemia events
Description
Assessed at each study visit
Time Frame
Entire 9-month study period
Title
Proportion experiencing acute pancreatitis events
Description
Assessed at each study visit
Time Frame
Entire 9-month study period
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
- Age ≥ 18 years
- BMI 25-45 kg/m2
- T2DM
- Advanced CKD* (last eGFR <30 ml/min/1.73m2 in EHR or ESKD on dialysis prior to screening) or stage G3B/A2-3 CKD (eGFR 30 to <45 ml/min/1.73m2 with albumin/creatinine ratio >30 mg/g).
- Fulfill kidney transplant listing criteria except for one or more of the following reasons (1: uncontrolled diabetes [A1c ≥9%); 2: severe obesity (BMI ≥ 40 kg/m2 or BMI 35-40 kg/m2 with waist circumference >120 cm). See exclusion criteria for general contraindications used for transplant listing used by majority of U.S. transplant centers].
- Ability to provide informed consent before any trial-related activities
- Access to a telephone
The cause of the CKD does not need to be due specifically to diabetes
Exclusion Criteria (General contraindications used for transplant listing used by majority of U.S. transplant centers)
- Active malignancy
- History of pancreatitis
- Active substance abuse
- Severe COPD
- Pulmonary fibrosis
- Symptomatic angina or recent myocardial infarction within 6 months
- Severe peripheral vascular disease
- Cirrhosis
- New York Health Association (NYHA) Class III-IV congestive heart failure
- Severe cognitive impairment
- Drug addiction
- History of non-adherence to therapy
- Active infection
- Expected life expectancy < 5 years
Additional exclusion criteria
- Type 1 diabetes mellitus
- History of diabetic ketoacidosis within the last 12 months
- Planning on undergoing bariatric surgery in next 9 months.
- Pregnant, breast-feeding, or planned pregnancy prior to the end of participation or not using adequate contraceptive measures
- Self-reported average consumption of > 21 alcoholic beverages per week or binge drinking
- Psychiatric hospitalization in past year
- Principal investigator discretion (i.e. concerns about safety, compliance)
- Known or suspected allergy to trial medication
- Previous participation (i.e. randomized) in this trial
- Use of GLP1-RA or pramlintide within 90 days prior to screening
- Use of metformin (contraindicated with eGFR < 30 ml/min/1.73m2)
- Use of DPP-4 inhibitors within 30 days prior to screening
- Personal or family history of medullary thyroid cancer, multiple endocrine neoplasia types 2A and 2B syndrome
- Last hemoglobin A1c ≥ 12% or A1c <6% (to avoid risk of hypoglycemia) prior to screening
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alex R Chang, MD, MS
Organizational Affiliation
Geisinger Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Geisinger Medical Center
City
Danville
State/Province
Pennsylvania
ZIP/Postal Code
17821
Country
United States
Facility Name
Geisinger Wyoming Valley
City
Wilkes-Barre
State/Province
Pennsylvania
ZIP/Postal Code
18702
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Time Frame
Data will become available at the time of publication of the main trial results and will be publicly available indefinitely.
IPD Sharing Access Criteria
The deidentified IPD will be publicly available without restrictions.
Learn more about this trial
Effect of Subcutaneous Semaglutide on Kidney Transplant Candidacy
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