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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

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.

Condition or disease Intervention/treatment Phase
Diabetes Mellitus, Type 2 Obesity Drug: canagliflozin Drug: Placebo (for canagliflozin) Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 16 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Canagliflozin vs. Placebo for Post Bariatric Patients With Persistent Type 2 Diabetes
Actual Study Start Date : January 5, 2017
Actual Primary Completion Date : July 19, 2018
Actual Study Completion Date : July 19, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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).
Drug: canagliflozin
encapsulated (gelatin capsule).
Other Name: Invokana

Placebo Comparator: Placebo
Subjects randomized to placebo will be assigned a six month course of one placebo pill daily (n =12).
Drug: Placebo (for canagliflozin)
encapsulated (gelatin capsule). The placebo capsule filler is called micro-crystalline cellulose.




Primary Outcome Measures :
  1. 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 (%)


Secondary Outcome Measures :
  1. 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.

  2. 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

  3. 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 ]
  4. 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

  5. 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

  6. 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

  7. 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

  8. 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)

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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



Information from the National Library of Medicine

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Ages Eligible for Study:   20 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

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): NCT02912455


Locations
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United States, Ohio
Cleveland Clinic
Cleveland, Ohio, United States, 44195
Sponsors and Collaborators
The Cleveland Clinic
Janssen Scientific Affairs, LLC
Investigators
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Principal Investigator: Sangeeta Kashyap, MD The Cleveland Clinic
  Study Documents (Full-Text)

Documents provided by Sangeeta Kashyap, The Cleveland Clinic:
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Responsible Party: Sangeeta Kashyap, Associate Professor of Medicine, The Cleveland Clinic
ClinicalTrials.gov Identifier: NCT02912455    
Other Study ID Numbers: 16-574
First Posted: September 23, 2016    Key Record Dates
Results First Posted: June 30, 2020
Last Update Posted: June 30, 2020
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Sangeeta Kashyap, The Cleveland Clinic:
Post-Bariatric Surgery
hemoglobin A1c protein, human
Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Canagliflozin
Sodium-Glucose Transporter 2 Inhibitors
Molecular Mechanisms of Pharmacological Action
Hypoglycemic Agents
Physiological Effects of Drugs