Clinical trial NCT02912455: CARAT: Canagliflozin vs. Placebo for Post Bariatric Patients With Persistent Type 2 Diabetes
Official title: Canagliflozin vs. Placebo for Post Bariatric Patients With Persistent Type 2 Diabetes
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Diabetes Mellitus, Type 2
Obesity
Keywords: Post-Bariatric Surgery
hemoglobin A1c protein, human
Lead sponsor: The Cleveland Clinic
Sponsor class: OTHER
Collaborators: name: Janssen Scientific Affairs, LLC
First posted: 2016-09-23
Enrollment: 16
Sex: ALL
Minimum age (years): 20
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Change at Six Months Versus Baseline in Hemoglobin A1c Value (%)
timeFrame: 6 months
Secondary outcomes:
measure: Change in Fasting Glucose From Randomization
timeFrame: 6 months
measure: Change in Body Weight at Six Months Compared to Baseline
timeFrame: 6 months
measure: Change in Total Cholesterol
timeFrame: 6 months
measure: Change in Diastolic Blood Pressure at Six Months Compared to Baseline
timeFrame: 6 months
measure: Change in Adiponectin Levels at 6 Months Compared to Randomization
timeFrame: 6 months
measure: Change in Leptin Levels at 6 Months Compared to Baseline
timeFrame: 6 months
measure: Change in CRP Levels at 6 Months Compared to Baseline
timeFrame: 6 months
measure: Number of Participants Who Reported Hypoglycemia From Each Group (at a Frequency of 1 Episode)
timeFrame: 6 months
measure: Change in Percent Body Fat as Measured by DEXA Scan at 6 Months Compared to Randomization
timeFrame: 6 months
measure: Change in Systolic Blood Pressure at 6 Months Compared to Baseline
timeFrame: 6 months
measure: Change in Percentage of Lean Mass
timeFrame: 6 months
measure: Change in Percentage of Truncal Fat
timeFrame: 6 months
measure: Change in Percentage of Android Fat
timeFrame: 6 months
measure: Change in Percentage of Gynoid Fat
timeFrame: 6 months
measure: Change in Spine Bone Mineral Density
timeFrame: 6 months
measure: Change in Leg Bone Mineral Density
timeFrame: 6 months
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
Study officials:
affiliation: The Cleveland Clinic
name: Sangeeta Kashyap, MD
role: PRINCIPAL_INVESTIGATOR
References: