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CARAT: Canagliflozin vs. Placebo for Post Bariatric Patients With Persistent Type 2 Diabetes

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02912455
Recruitment Status : Terminated (Study was terminated due to difficulty with reaching enrollment goals)
First Posted : September 23, 2016
Results First Posted : June 30, 2020
Last Update Posted : June 30, 2020
Sponsor:
Collaborator:
Janssen Scientific Affairs, LLC
Information provided by (Responsible Party):
Sangeeta Kashyap, The Cleveland Clinic

Tracking Information
First Submitted Date  ICMJE August 24, 2016
First Posted Date  ICMJE September 23, 2016
Results First Submitted Date  ICMJE November 12, 2019
Results First Posted Date  ICMJE June 30, 2020
Last Update Posted Date June 30, 2020
Actual Study Start Date  ICMJE January 5, 2017
Actual Primary Completion Date July 19, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 17, 2020)
The Change in Hemoglobin A1c From Randomization Following the 6 Month Administration of Canagliflozin vs. Placebo in Patients With Type 2 Diabetes Post-bariatric Surgery [ Time Frame: 6 months ]
Actual change at six months versus baseline in hemoglobin A1c value (%)
Original Primary Outcome Measures  ICMJE
 (submitted: September 21, 2016)
Percent of subjects with normal Hemoglobin A1c (≤6.5%) after 6 month administration of canagliflozin vs. placebo in patients with type 2 diabetes post-bariatric surgery [ Time Frame: 6 months ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 17, 2020)
  • Change in Fasting Glucose From Randomization [ Time Frame: 6 months ]
    The change in fasting glucose from randomization following the 6 month administration of canagliflozin vs. placebo in patients with type 2 diabetes post-bariatric surgery.
  • The Change in Body Weight From Randomization Following the 6 Month Administration of Canagliflozin vs. Placebo in Patients With Type 2 Diabetes Post-bariatric Surgery. [ Time Frame: 6 months ]
    Change in body weight at six months compared to baseline
  • The Change in Total Cholesterol From Randomization Following the 6 Month Administration of Canagliflozin vs. Placebo in Patients With Type 2 Diabetes Post-bariatric Surgery. [ Time Frame: 6 months ]
  • The Change in Diastolic Blood Pressure From Randomization Following the 6 Month Administration of Canagliflozin vs. Placebo in Patients With Type 2 Diabetes Post-bariatric Surgery [ Time Frame: 6 months ]
    Change in diastolic blood pressure at six months compared to baseline
  • The Change in Adiponectin Levels From Randomization Following the 6 Month Administration of Canagliflozin vs. Placebo in Patients With Type 2 Diabetes Post-bariatric Surgery. [ Time Frame: 6 months ]
    Change in adiponectin levels at 6 months compared to randomization
  • The Change in Leptin Levels From Randomization Following the 6 Month Administration of Canagliflozin vs. Placebo in Patients With Type 2 Diabetes Post-bariatric Surgery. [ Time Frame: 6 months ]
    Change in leptin levels at 6 months compared to baseline
  • The Change in C-reactive Protein Levels From Randomization Following the 6 Month Administration of Canagliflozin vs. Placebo in Patients With Type 2 Diabetes Post-bariatric Surgery. [ Time Frame: 6 months ]
    Change in CRP levels at 6 months compared to baseline
  • The Number of Symptomatic Hypoglycemia Episodes From Randomization Following the 6 Month Administration of Canagliflozin vs. Placebo in Patients With Type 2 Diabetes Post-bariatric Surgery. [ Time Frame: 6 months ]
    Number of participants who reported hypoglycemia from each group (at a frequency of 1 episode)
  • The Change in Body Fat From Randomization Following the 6 Month Administration of Canagliflozin vs. Placebo in Patients With Type 2 Diabetes Post-bariatric Surgery. [ Time Frame: 6 months ]
    Change in percent body fat as measured by DEXA scan at 6 months compared to randomization
  • The Change in Systolic Blood Pressure From Randomization Following the 6 Month Administration of Canagliflozin vs. Placebo in Patients With Type 2 Diabetes Post-bariatric Surgery [ Time Frame: 6 months ]
    Change in systolic blood pressure at 6 months compared to baseline
  • Change in Percentage of Lean Mass [ Time Frame: 6 months ]
    Change in percentage of lean body mass as measured by DEXA scan at 6 months compared to randomization
  • Change in Percentage of Truncal Fat [ Time Frame: 6 months ]
    Change in percentage of truncal fat as measured by DEXA scan at 6 months compared to randomization
  • Change in Percentage of Android Fat [ Time Frame: 6 months ]
    Change in percentage of android fat as measured by DEXA scan at 6 months compared to randomization
  • Change in Percentage of Gynoid Fat [ Time Frame: 6 months ]
    Change in percentage of gynoid fat as measured by DEXA scan at 6 months compared to randomization
  • Change in Spine Bone Mineral Density [ Time Frame: 6 months ]
    Change in spine bone marrow density as measured by DEXA scan at 6 months compared to randomization
  • Change in Leg Bone Mineral Density [ Time Frame: 6 months ]
    Change in leg bone marrow density as measured by DEXA scan at 6 months compared to randomization
Original Secondary Outcome Measures  ICMJE
 (submitted: September 21, 2016)
  • The change in Hemoglobin A1c from baseline following the 6 month administration of canagliflozin vs. placebo in patients with type 2 diabetes post-bariatric surgery. [ Time Frame: 6 months ]
  • The change in fasting glucose from randomization following the 6 month administration of canagliflozin vs. placebo in patients with type 2 diabetes post-bariatric surgery. [ Time Frame: 6 months ]
  • The Change in Body Weight From Randomization Following the 6 Month Administration of Canagliflozin vs. Placebo in Patients With Type 2 Diabetes Post-bariatric Surgery. [ Time Frame: 6 months ]
  • The Change in Total Cholesterol From Randomization Following the 6 Month Administration of Canagliflozin vs. Placebo in Patients With Type 2 Diabetes Post-bariatric Surgery. [ Time Frame: 6 months ]
  • The change in diastolic and systolic blood pressure from randomization following the 6 month administration of canagliflozin vs. placebo in patients with type 2 diabetes post-bariatric surgery [ Time Frame: 6 months ]
  • The Change in Adiponectin Levels From Randomization Following the 6 Month Administration of Canagliflozin vs. Placebo in Patients With Type 2 Diabetes Post-bariatric Surgery. [ Time Frame: 6 months ]
  • The Change in Leptin Levels From Randomization Following the 6 Month Administration of Canagliflozin vs. Placebo in Patients With Type 2 Diabetes Post-bariatric Surgery. [ Time Frame: 6 months ]
  • The Change in C-reactive Protein Levels From Randomization Following the 6 Month Administration of Canagliflozin vs. Placebo in Patients With Type 2 Diabetes Post-bariatric Surgery. [ Time Frame: 6 months ]
  • The Number of Symptomatic Hypoglycemia Episodes From Randomization Following the 6 Month Administration of Canagliflozin vs. Placebo in Patients With Type 2 Diabetes Post-bariatric Surgery. [ Time Frame: 6 months ]
  • The change in DXA scan results from randomization following the 6 month administration of canagliflozin vs. placebo in patients with type 2 diabetes post-bariatric surgery. [ Time Frame: 6 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE CARAT: Canagliflozin vs. Placebo for Post Bariatric Patients With Persistent Type 2 Diabetes
Official Title  ICMJE Canagliflozin vs. Placebo for Post Bariatric Patients With Persistent Type 2 Diabetes
Brief Summary This is a prospective, randomized clinical trial for patients with recurrent type 2 diabetes post-gastric bypass surgery that will compare a 6 month course of canagliflozin monotherapy vs. placebo on clinical outcomes of type 2 diabetes.
Detailed Description

Following consent and a screening visit to assess eligibility and clinical status (i.e. historical, physical and biochemical parameters including glycemic control and a pregnancy test in females), a baseline visit with diabetes educator will take place to provide standard diabetes education, nutrition and exercise prescription.

Nutritional assessment for vitamin/mineral deficiency will be performed per clinical care guidelines at the screening visit. Subjects will be asked to take nutritional supplements (i.e. vitamins and minerals) per current clinical guidelines for post-bariatric patients. Stable doses of supplements will be established for at least 2 weeks prior to randomization. Thirty-six subjects with recurrent diabetes that are naïve to hypoglycemic agents with HbA1c greater than or equal to 6.5% and less than 10% will be randomly assigned to a six month course of a) canagliflozin 100mg for 2 weeks titrated up to 300 mg daily (N = 24) vs. placebo (n= 12) at the randomization. Patients taking an anti-diabetic medication will be asked to wash out for 8 weeks prior to the randomization visit. At randomization, biochemical assessment of glycemic parameters (fasting glucose, HbA1c), lipid panel, complete metabolic panel, uric acid, leptin, total and HMW adiponectin, C-reactive protein and urine for albumin/creatinine ratio will be performed. Dual-energy x-ray absorptiometry (DXA) scan will be performed for body fat composition.

Following randomization, subjects will be clinically evaluated at three office visits at 6 weeks, 3 and 6 months by PI and/or the research staff. The primary outcome measures at 6 months post-randomization include HbA1c followed by the change in HbA1c from randomization. Secondary measures include fasting glucose, BMI, change in body weight, blood pressure, lipid profile. Symptomatic hypoglycemia (blood glucose < 70) and drug related side effects (i.e. mycotic genital infections, urinary tract infection) will be monitored with adverse event reporting. Metabolic testing in all subjects at randomization and at 6 months will include a DXA scan for body fat composition and blood for leptin and adiponectin levels.

Rescue glucose lowering therapy will be provided for the control group for blood glucose >250 mg/dl. If chronic uncontrolled hyperglycemia (HbA1c >10%) occurs then basal bolus insulin will be implemented.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Diabetes Mellitus, Type 2
  • Obesity
Intervention  ICMJE
  • Drug: canagliflozin
    encapsulated (gelatin capsule).
    Other Name: Invokana
  • Drug: Placebo (for canagliflozin)
    encapsulated (gelatin capsule). The placebo capsule filler is called micro-crystalline cellulose.
Study Arms  ICMJE
  • Active Comparator: Study Drug (canagliflozin)
    Subjects randomized to study drug will be assigned a six month course starting on canagliflozin 100 mg for two weeks titrated up to 300 mg daily (n= 24).
    Intervention: Drug: canagliflozin
  • Placebo Comparator: Placebo
    Subjects randomized to placebo will be assigned a six month course of one placebo pill daily (n =12).
    Intervention: Drug: Placebo (for canagliflozin)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: March 1, 2019)
16
Original Estimated Enrollment  ICMJE
 (submitted: September 21, 2016)
36
Actual Study Completion Date  ICMJE July 19, 2018
Actual Primary Completion Date July 19, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Post Roux-n-Y gastric bypass (RYGB) surgery and sleeve gastrectomy (SG) patients who underwent surgery >1 and <15 years ago in the Cleveland surrounding area
  • Age 20-75 years of age
  • Type II Diabetes Mellitus (D2M) diagnosis (history, medication usage, biochemical criteria) prior to and after surgery; after surgery, defined by a single HbA1c of greater or equal to 6.5% at consent and screening.
  • Metformin patients must have an HbA1c greater than or equal to 6.5% but less than or equal to 10% at randomization; for diet controlled patients (i.e. not on any T2D medication), HbA1c must be greater than or equal to 6.5% at randomization.
  • Patient reporting of improvement in T2D status or objective improvements in T2D status at any time post-surgery.
  • estimated glomerular filtration rate (eGFR) ≥ 60mL/min prior to randomization
  • Has the ability and willingness to provide informed consent.
  • Is able to understand the options and to comply with the requirements of each program
  • Female subject agrees to have a serum pregnancy test at screening. A negative serum pregnancy test result is required prior to randomization.
  • Female patients must agree to use a reliable method of contraception for 6 months or duration of intervention
  • Patients taking an anti-diabetic medication, except insulin, are eligible and must agree to washout for 8 weeks prior to the randomization visit.

Exclusion Criteria:

  • Type 1 diabetes indicated by history of diabetic ketoacidosis and lack of remission in response to bariatric surgery
  • Other post bariatric procedures (banding, duodenal switch, biliopancreatic diversion)
  • Current use of insulin.
  • End organ diabetic complications (renal failure, cardiomyopathy, severe neuropathy/foot ulcers)
  • Documented severe or unstable depression/anxiety or eating disorder that would not enable patient to adhere to anti-diabetic treatment
  • Clinical contraindications to use canagliflozin, i.e., history of bladder cancer, Child-Pugh class C
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 20 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02912455
Other Study ID Numbers  ICMJE 16-574
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Sangeeta Kashyap, The Cleveland Clinic
Study Sponsor  ICMJE The Cleveland Clinic
Collaborators  ICMJE Janssen Scientific Affairs, LLC
Investigators  ICMJE
Principal Investigator: Sangeeta Kashyap, MD The Cleveland Clinic
PRS Account The Cleveland Clinic
Verification Date June 2020

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