Diabetes Mellitus, Type 2Phase 4NCT02912455
CARAT: Canagliflozin vs. Placebo for Post Bariatric Patients With Persistent Type 2 Diabetes
A Phase 4 study testing canagliflozin in people with Diabetes Mellitus, Type 2 and Obesity, run by The Cleveland Clinic at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 20 to 75 years
- Conditions the study is for
- Diabetes Mellitus, Type 2, Obesity
- What is being tested?
- canagliflozin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- 5 Jan 2017to 19 Jul 2018
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 11Show fewer
- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Canagliflozin vs. Placebo for Post Bariatric Patients With Persistent Type 2 Diabetes
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.
Read the 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.
- Conditions
- Diabetes Mellitus, Type 2, Obesity
- Being tested
- canagliflozin, Placebo (for canagliflozin)
- Keywords
- Post-Bariatric Surgery, hemoglobin A1c protein, human
- Medical subject headings
- Diabetes Mellitus, Type 2, Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
canagliflozinDrug
Also called Invokana
encapsulated (gelatin capsule).
Placebo (for canagliflozin)Drug
encapsulated (gelatin capsule). The placebo capsule filler is called micro-crystalline cellulose.
| Study group | Role | What they receive |
|---|---|---|
| Study Drug (canagliflozin) | Active comparator | 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). Receives: Drug: canagliflozin |
| Placebo | Placebo comparator | Subjects randomized to placebo will be assigned a six month course of one placebo pill daily (n =12). Receives: Drug: Placebo (for canagliflozin) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change at Six Months Versus Baseline in Hemoglobin A1c Value (%)
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
Measured: 6 months
Secondary outcomes (16)
Change in Fasting Glucose From Randomization
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.
Measured: 6 months
Change in Body Weight at Six Months Compared to Baseline
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.
Measured: 6 months
Change in Total Cholesterol
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
Measured: 6 months
Change in Diastolic Blood Pressure at Six Months Compared to Baseline
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
Measured: 6 months
Change in Adiponectin Levels at 6 Months Compared to Randomization
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.
Measured: 6 months
Change in Leptin Levels at 6 Months Compared to Baseline
Change in leptin levels at 6 months compared to baseline 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.
Measured: 6 months
Change in CRP 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.
Measured: 6 months
Number of Participants Who Reported Hypoglycemia From Each Group (at a Frequency of 1 Episode)
The number of participants who reported symptomatic hypoglycemia episodes from randomization following the 6 month administration of canagliflozin vs. placebo in patients with type 2 diabetes post-bariatric surgery.
Measured: 6 months
Change in Percent Body Fat as Measured by DEXA Scan at 6 Months Compared to Randomization
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.
Measured: 6 months
Change in Systolic Blood Pressure at 6 Months Compared to Baseline
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
Measured: 6 months
Change in Percentage of Lean Mass
Change in percentage of lean body mass as measured by DEXA scan at 6 months compared to randomization
Measured: 6 months
Change in Percentage of Truncal Fat
Change in percentage of truncal fat as measured by DEXA scan at 6 months compared to randomization
Measured: 6 months
Change in Percentage of Android Fat
Change in percentage of android fat as measured by DEXA scan at 6 months compared to randomization
Measured: 6 months
Change in Percentage of Gynoid Fat
Change in percentage of gynoid fat as measured by DEXA scan at 6 months compared to randomization
Measured: 6 months
Change in Spine Bone Mineral Density
Change in spine bone marrow density as measured by DEXA scan at 6 months compared to randomization
Measured: 6 months
Change in Leg Bone Mineral Density
Change in leg bone marrow density as measured by DEXA scan at 6 months compared to randomization
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Sep 2016 (estimated)
- Study start5 Jan 2017
- Primary completion19 Jul 2018
- Study completion19 Jul 2018
Why it stopped: Study was terminated due to difficulty with reaching enrollment goals
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Diabetes Mellitus, Type 2Studies of the same condition, open and under way.
- More trials run by The Cleveland ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Cleveland Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- Janssen Scientific Affairs, LLC
- Responsible party
- Principal investigator, Sangeeta Kashyap, The Cleveland Clinic
- Investigators
- Sangeeta Kashyap, MD, Principal investigator, The Cleveland Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02912455
- Sponsor's protocol ID
- 16-574
- Status last verified
- Oct 2020
- First submitted
- 24 Aug 2016
- Last updated
- 20 Nov 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Canagliflozin vs. Placebo for Post Bariatric Patients With Persistent Type 2 Diabetes
- ClinicalTrials.gov ID
- NCT02912455
- Acronym / sponsor ID
- 16-574
- Conditions
- Diabetes Mellitus, Type 2, Obesity
- Keywords
- Post-Bariatric Surgery, hemoglobin A1c protein, human
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study was terminated due to difficulty with reaching enrollment goals
- Enrolment
- 16 participants (actual)
- Lead sponsor
- The Cleveland ClinicUniversity, hospital or other
- Collaborators
- Janssen Scientific Affairs, LLC
- Study start
- 5 Jan 2017 (actual)
- Primary completion
- 19 Jul 2018 (actual)
- Study completion
- 19 Jul 2018 (actual)
- First posted
- 23 Sep 2016 (estimated)
- Results
- Posted 30 Jun 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Study Drug (canagliflozin) | Active comparator | Drug: canagliflozinSubjects 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). |
| Placebo | Placebo comparator | Drug: Placebo (for canagliflozin)Subjects randomized to placebo will be assigned a six month course of one placebo pill daily (n =12). |
Who may qualify
- Ages
- 20 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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.
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| canagliflozinAlso: Invokanaencapsulated (gelatin capsule). | Drug | Study Drug (canagliflozin) |
| Placebo (for canagliflozin)encapsulated (gelatin capsule). The placebo capsule filler is called micro-crystalline cellulose. | Drug | Placebo |
Primary outcome
Change at Six Months Versus Baseline in Hemoglobin A1c Value (%)
Time frame: 6 months
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
16 secondary outcomes
Change in Fasting Glucose From Randomization
Time frame: 6 months
Change in Body Weight at Six Months Compared to Baseline
Time frame: 6 months
Change in Total Cholesterol
Time frame: 6 months
Change in Diastolic Blood Pressure at Six Months Compared to Baseline
Time frame: 6 months
Change in Adiponectin Levels at 6 Months Compared to Randomization
Time frame: 6 months
Change in Leptin Levels at 6 Months Compared to Baseline
Time frame: 6 months
Change in CRP Levels at 6 Months Compared to Baseline
Time frame: 6 months
Number of Participants Who Reported Hypoglycemia From Each Group (at a Frequency of 1 Episode)
Time frame: 6 months
Change in Percent Body Fat as Measured by DEXA Scan at 6 Months Compared to Randomization
Time frame: 6 months
Change in Systolic Blood Pressure at 6 Months Compared to Baseline
Time frame: 6 months
Change in Percentage of Lean Mass
Time frame: 6 months
Change in Percentage of Truncal Fat
Time frame: 6 months
Change in Percentage of Android Fat
Time frame: 6 months
Change in Percentage of Gynoid Fat
Time frame: 6 months
Change in Spine Bone Mineral Density
Time frame: 6 months
Change in Leg Bone Mineral Density
Time frame: 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Nov 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sangeeta Kashyap, MD principal investigator
The Cleveland Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing canagliflozin in people with Diabetes Mellitus, Type 2 and Obesity, run by The Cleveland Clinic at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 20 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Jun 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change at Six Months Versus Baseline in Hemoglobin A1c Value (%) (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Nov 2020.