Diabetes Mellitus, Type 2Phase 4NCT02624908
Canagliflozin-Mealtime Insulin Rescue
A Phase 4 study testing canagliflozin in people with Diabetes Mellitus, Type 2, run by Foundation for Atlanta Veterans Education and Research, Inc. at 1 site in United States.
Trial summary
24-week, randomized, double blind, placebo-controlled trial to evaluate safety and efficacy of canagliflozin as compared with placebo in reducing the need for mealtime insulin in subjects with type 2 diabetes currently using a basal-bolus insulin regimen. Read more about this study
- Who is it for?
- Ages 30 to 70 years
- Conditions the study is for
- Diabetes Mellitus, Type 2
- 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
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2016to Dec 2022
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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 30 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- use of basal-bolus insulin
- onset of diabetes after age 30
- BMI less than 35
- eGFR at least 60 ml/mn
- Hb A1c 7.0-10.0%
- willingness to perform home glucose monitoring
- willingness to transmit glucose and medication information weekly
Who cannot join
- Type 1 diabetes
- Known peripheral artery disease
- Liver enzymes equal or more than 1.5 times the upper limit of normal
- Chronic heart failure NYHA class III or IV
- Current haemodialysis or peritoneal dialysis
- End stage liver disease, defined as acute or chronic liver disease and recent history of one of the following: ascites, encephalopathy, variceal bleeding, bilirubin equal or greater than 2.0 mg/dL, albumin equal or less than 3.5 g/ dL, prothrombin time greater or equal to 4 seconds, INR greater than or equal to 1.7 or prior liver transplant
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- Known or suspected hypersensitivity to trial products or related products
- Female of child-bearing potential who is pregnant, breast-feeding or intends to become pregnant or is not using adequate contraceptive methods as required by law or local practice.
- Expected simultaneous participation in any other clinical trial of an investigational medicinal product.
- Receipt of any investigational medicinal product within 30 days before randomization
- Current or past (within the last 5 years) malignant neoplasms (except basal cell and squamous cell skin carcinoma)
- Any condition that in the investigator's opinion would make the subject unable to adhere to the trial visit schedule and procedures
- Known history of non-compliance to treatment.
Trial locations and contacts
1 site in 1 country.
About this study
24-week, randomized, double blind, placebo-controlled trial to evaluate safety and efficacy of canagliflozin as compared with placebo in reducing the need for mealtime insulin in subjects with type 2 diabetes currently using a basal-bolus insulin regimen.
Read the detailed description
The Canagliflozin Mealtime Insulin Rescue study will enroll up to 40 subjects at the Atlanta VA Medical Center. Subjects will be screened and enter a 2-week run-in period during which they will switch to or continue on a diabetes treatment regimen of basal insulin before supper and aspart insulin before meals. Run-in will be useful in evaluating compliance to treatment and self-monitoring. After run-in, subjects will collect one week of baseline glycemic data with regular pre-meal and fasting glycemic levels using both finger stick testing and continuous glucose monitoring.
Subjects will be randomized at Visit 3 to 100 mg of canagliflozin or placebo. If well tolerated, this dose will be increased to 300 mg of canagliflozin or placebo at Visit 4.
Diabetes management will be assured through regular contact with the study team (weekly calls and clinic visits at Weeks 4, 8, 16 and 24). Management will be facilitated by diabetes management software. Self-monitoring and continuous glucose monitoring will be repeated at the end of study participation.
- Conditions
- Diabetes Mellitus, Type 2
- Being tested
- canagliflozin, placebo
- Medical subject headings
- Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
canagliflozinDrug
Also called Invokana
Subjects randomized to active drug will receive canagliflozin 100 mg . If study drug well tolerated, dose will be increased to 300 mg canagliflozin at Visit 4.
placeboDrug
Also called inactive substance
Subjects randomized to placebo will receive 100 mg placebo pill . If study drug well tolerated, dose will be increased to 300 mg placebo pill at Visit 4.
| Study group | Role | What they receive |
|---|---|---|
| canagliflozin | Active comparator | Subjects randomized to this arm will start with 100 mg tablet and increase to 300 mg tablet at Visit 4 if well tolerated. Receives: Drug: canagliflozin |
| placebo | Placebo comparator | Subjects randomized to this arm will start with 100 mg tablet and increase to 300 mg tablet at Visit 4 if well tolerated. Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of patients who discontinue all pre-meal medications for at least one meal per day
Measured: 24 weeks
Number of patients who replace mealtime insulin with an oral agent for at least one meal per day
anti-hyperglycemic pill instead of insulin for at least one meal per day
Measured: 24 weeks
Number of patients with a continuing need for insulin 4 times per day
no change from the original basal -bolus regimen
Measured: 24 weeks
Frequency and severity of hypoglycemia
Hypoglycemic episodes will be evaluated using a hypoglycemia questionnaire
Measured: 24 weeks
Self monitoring and continuous monitoring blood glucose levels
glycemic control and glycemic variability
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Dec 2015 (estimated)
- Study startJan 2016
- Primary completionJul 2018
- Study completionDec 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for Diabetes Mellitus, Type 2Studies of the same condition, open and under way.
- 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
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Foundation for Atlanta Veterans Education and Research, Inc.
- Sponsor type
- University, hospital or other
- Collaborators
- Janssen Scientific Affairs, LLC
- Responsible party
- Sponsor
- Investigators
- Lawrence S Phillips, MD, Principal investigator, Atlanta VA Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02624908
- Sponsor's protocol ID
- 28431754DIA4008
- Status last verified
- Aug 2022
- First submitted
- 3 Dec 2015
- Last updated
- 15 Aug 2022
- Results posted
- No
- Data monitoring committee
- Yes
Publications
ORIGIN Trial Investigators; Gerstein HC, Bosch J, Dagenais GR, Diaz R, Jung H, Maggioni AP, Pogue J, Probstfield J, Ramachandran A, Riddle MC, Ryden LE, Yusuf S. Basal insulin and cardiovascular and other outcomes in dysglycemia. N Engl J Med. 2012 Jul 26;367(4):319-28. doi: 10.1056/NEJMoa1203858. Epub 2012 Jun 11.
PubMed 22686416Bretzel RG, Nuber U, Landgraf W, Owens DR, Bradley C, Linn T. Once-daily basal insulin glargine versus thrice-daily prandial insulin lispro in people with type 2 diabetes on oral hypoglycaemic agents (APOLLO): an open randomised controlled trial. Lancet. 2008 Mar 29;371(9618):1073-84. doi: 10.1016/S0140-6736(08)60485-7.
PubMed 18374840Schernthaner G, Gross JL, Rosenstock J, Guarisco M, Fu M, Yee J, Kawaguchi M, Canovatchel W, Meininger G. Canagliflozin compared with sitagliptin for patients with type 2 diabetes who do not have adequate glycemic control with metformin plus sulfonylurea: a 52-week randomized trial. Diabetes Care. 2013 Sep;36(9):2508-15. doi: 10.2337/dc12-2491. Epub 2013 Apr 5.
PubMed 23564919Polidori D, Sha S, Mudaliar S, Ciaraldi TP, Ghosh A, Vaccaro N, Farrell K, Rothenberg P, Henry RR. Canagliflozin lowers postprandial glucose and insulin by delaying intestinal glucose absorption in addition to increasing urinary glucose excretion: results of a randomized, placebo-controlled study. Diabetes Care. 2013 Aug;36(8):2154-61. doi: 10.2337/dc12-2391. Epub 2013 Feb 14.
PubMed 23412078Budnitz DS, Lovegrove MC, Shehab N, Richards CL. Emergency hospitalizations for adverse drug events in older Americans. N Engl J Med. 2011 Nov 24;365(21):2002-12. doi: 10.1056/NEJMsa1103053.
PubMed 22111719Home PD, Fritsche A, Schinzel S, Massi-Benedetti M. Meta-analysis of individual patient data to assess the risk of hypoglycaemia in people with type 2 diabetes using NPH insulin or insulin glargine. Diabetes Obes Metab. 2010 Sep;12(9):772-9. doi: 10.1111/j.1463-1326.2010.01232.x.
PubMed 20649629Johnston SS, Conner C, Aagren M, Smith DM, Bouchard J, Brett J. Evidence linking hypoglycemic events to an increased risk of acute cardiovascular events in patients with type 2 diabetes. Diabetes Care. 2011 May;34(5):1164-70. doi: 10.2337/dc10-1915. Epub 2011 Mar 18.
PubMed 21421802NICE-SUGAR Study Investigators; Finfer S, Liu B, Chittock DR, Norton R, Myburgh JA, McArthur C, Mitchell I, Foster D, Dhingra V, Henderson WR, Ronco JJ, Bellomo R, Cook D, McDonald E, Dodek P, Hebert PC, Heyland DK, Robinson BG. Hypoglycemia and risk of death in critically ill patients. N Engl J Med. 2012 Sep 20;367(12):1108-18. doi: 10.1056/NEJMoa1204942.
PubMed 22992074McCoy RG, Van Houten HK, Ziegenfuss JY, Shah ND, Wermers RA, Smith SA. Increased mortality of patients with diabetes reporting severe hypoglycemia. Diabetes Care. 2012 Sep;35(9):1897-901. doi: 10.2337/dc11-2054. Epub 2012 Jun 14.
PubMed 22699297Ceriello A, Esposito K, Piconi L, Ihnat MA, Thorpe JE, Testa R, Boemi M, Giugliano D. Oscillating glucose is more deleterious to endothelial function and oxidative stress than mean glucose in normal and type 2 diabetic patients. Diabetes. 2008 May;57(5):1349-54. doi: 10.2337/db08-0063. Epub 2008 Feb 25.
PubMed 18299315Brownlee M, Hirsch IB. Glycemic variability: a hemoglobin A1c-independent risk factor for diabetic complications. JAMA. 2006 Apr 12;295(14):1707-8. doi: 10.1001/jama.295.14.1707. No abstract available.
PubMed 16609094
Study at a glance
From the registry record, last updated by the sponsor on 15 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Canagliflozin-Mealtime Insulin Rescue
- ClinicalTrials.gov ID
- NCT02624908
- Acronym / sponsor ID
- 28431754DIA4008
- Conditions
- Diabetes Mellitus, Type 2
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Foundation for Atlanta Veterans Education and Research, Inc.University, hospital or other
- Collaborators
- Janssen Scientific Affairs, LLC
- Study start
- Jan 2016 (actual)
- Primary completion
- Jul 2018 (actual)
- Study completion
- Dec 2022 (estimated)
- First posted
- 9 Dec 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
24-week, randomized, double blind, placebo-controlled trial to evaluate safety and efficacy of canagliflozin as compared with placebo in reducing the need for mealtime insulin in subjects with type 2 diabetes currently using a basal-bolus insulin regimen.
Detailed description
The Canagliflozin Mealtime Insulin Rescue study will enroll up to 40 subjects at the Atlanta VA Medical Center. Subjects will be screened and enter a 2-week run-in period during which they will switch to or continue on a diabetes treatment regimen of basal insulin before supper and aspart insulin before meals. Run-in will be useful in evaluating compliance to treatment and self-monitoring. After run-in, subjects will collect one week of baseline glycemic data with regular pre-meal and fasting glycemic levels using both finger stick testing and continuous glucose monitoring.
Subjects will be randomized at Visit 3 to 100 mg of canagliflozin or placebo. If well tolerated, this dose will be increased to 300 mg of canagliflozin or placebo at Visit 4.
Diabetes management will be assured through regular contact with the study team (weekly calls and clinic visits at Weeks 4, 8, 16 and 24). Management will be facilitated by diabetes management software. Self-monitoring and continuous glucose monitoring will be repeated at the end of study participation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| canagliflozin | Active comparator | Drug: canagliflozinSubjects randomized to this arm will start with 100 mg tablet and increase to 300 mg tablet at Visit 4 if well tolerated. |
| placebo | Placebo comparator | Drug: placeboSubjects randomized to this arm will start with 100 mg tablet and increase to 300 mg tablet at Visit 4 if well tolerated. |
Who may qualify
- Ages
- 30 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- use of basal-bolus insulin
- onset of diabetes after age 30
- BMI less than 35
- eGFR at least 60 ml/mn
- Hb A1c 7.0-10.0%
Key exclusion criteria (13 listed)
- Type 1 diabetes
- Known peripheral artery disease
- Liver enzymes equal or more than 1.5 times the upper limit of normal
- Chronic heart failure NYHA class III or IV
- Current haemodialysis or peritoneal dialysis
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: InvokanaSubjects randomized to active drug will receive canagliflozin 100 mg . If study drug well tolerated, dose will be increased to 300 mg canagliflozin at Visit 4. | Drug | canagliflozin |
| placeboAlso: inactive substanceSubjects randomized to placebo will receive 100 mg placebo pill . If study drug well tolerated, dose will be increased to 300 mg placebo pill at Visit 4. | Drug | placebo |
Primary outcome
Number of patients who discontinue all pre-meal medications for at least one meal per day
Time frame: 24 weeks
Number of patients who replace mealtime insulin with an oral agent for at least one meal per day
Time frame: 24 weeks
anti-hyperglycemic pill instead of insulin for at least one meal per day
Number of patients with a continuing need for insulin 4 times per day
Time frame: 24 weeks
no change from the original basal -bolus regimen
Frequency and severity of hypoglycemia
Time frame: 24 weeks
Hypoglycemic episodes will be evaluated using a hypoglycemia questionnaire
Self monitoring and continuous monitoring blood glucose levels
Time frame: 24 weeks
glycemic control and glycemic variability
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Aug 2022.
- Background: PubMed 22686416ORIGIN Trial Investigators; Gerstein HC, Bosch J, Dagenais GR, Diaz R, Jung H, Maggioni AP, Pogue J, Probstfield J, Ramachandran A, Riddle MC, Ryden LE, Yusuf S. Basal insulin and cardiovascular and other outcomes in dysglycemia. N Engl J Med. 2012 Jul 26;367(4):319-28. doi: 10.1056/NEJMoa1203858. Epub 2012 Jun 11.
- Background: PubMed 18374840Bretzel RG, Nuber U, Landgraf W, Owens DR, Bradley C, Linn T. Once-daily basal insulin glargine versus thrice-daily prandial insulin lispro in people with type 2 diabetes on oral hypoglycaemic agents (APOLLO): an open randomised controlled trial. Lancet. 2008 Mar 29;371(9618):1073-84. doi: 10.1016/S0140-6736(08)60485-7.
- Background: PubMed 23564919Schernthaner G, Gross JL, Rosenstock J, Guarisco M, Fu M, Yee J, Kawaguchi M, Canovatchel W, Meininger G. Canagliflozin compared with sitagliptin for patients with type 2 diabetes who do not have adequate glycemic control with metformin plus sulfonylurea: a 52-week randomized trial. Diabetes Care. 2013 Sep;36(9):2508-15. doi: 10.2337/dc12-2491. Epub 2013 Apr 5.
- Background: PubMed 23412078Polidori D, Sha S, Mudaliar S, Ciaraldi TP, Ghosh A, Vaccaro N, Farrell K, Rothenberg P, Henry RR. Canagliflozin lowers postprandial glucose and insulin by delaying intestinal glucose absorption in addition to increasing urinary glucose excretion: results of a randomized, placebo-controlled study. Diabetes Care. 2013 Aug;36(8):2154-61. doi: 10.2337/dc12-2391. Epub 2013 Feb 14.
- Background: PubMed 22111719Budnitz DS, Lovegrove MC, Shehab N, Richards CL. Emergency hospitalizations for adverse drug events in older Americans. N Engl J Med. 2011 Nov 24;365(21):2002-12. doi: 10.1056/NEJMsa1103053.
- Background: PubMed 20649629Home PD, Fritsche A, Schinzel S, Massi-Benedetti M. Meta-analysis of individual patient data to assess the risk of hypoglycaemia in people with type 2 diabetes using NPH insulin or insulin glargine. Diabetes Obes Metab. 2010 Sep;12(9):772-9. doi: 10.1111/j.1463-1326.2010.01232.x.
- Background: PubMed 21421802Johnston SS, Conner C, Aagren M, Smith DM, Bouchard J, Brett J. Evidence linking hypoglycemic events to an increased risk of acute cardiovascular events in patients with type 2 diabetes. Diabetes Care. 2011 May;34(5):1164-70. doi: 10.2337/dc10-1915. Epub 2011 Mar 18.
- Background: PubMed 22992074NICE-SUGAR Study Investigators; Finfer S, Liu B, Chittock DR, Norton R, Myburgh JA, McArthur C, Mitchell I, Foster D, Dhingra V, Henderson WR, Ronco JJ, Bellomo R, Cook D, McDonald E, Dodek P, Hebert PC, Heyland DK, Robinson BG. Hypoglycemia and risk of death in critically ill patients. N Engl J Med. 2012 Sep 20;367(12):1108-18. doi: 10.1056/NEJMoa1204942.
- Background: PubMed 22699297McCoy RG, Van Houten HK, Ziegenfuss JY, Shah ND, Wermers RA, Smith SA. Increased mortality of patients with diabetes reporting severe hypoglycemia. Diabetes Care. 2012 Sep;35(9):1897-901. doi: 10.2337/dc11-2054. Epub 2012 Jun 14.
- Background: PubMed 18299315Ceriello A, Esposito K, Piconi L, Ihnat MA, Thorpe JE, Testa R, Boemi M, Giugliano D. Oscillating glucose is more deleterious to endothelial function and oxidative stress than mean glucose in normal and type 2 diabetic patients. Diabetes. 2008 May;57(5):1349-54. doi: 10.2337/db08-0063. Epub 2008 Feb 25.
- Background: PubMed 16609094Brownlee M, Hirsch IB. Glycemic variability: a hemoglobin A1c-independent risk factor for diabetic complications. JAMA. 2006 Apr 12;295(14):1707-8. doi: 10.1001/jama.295.14.1707. No abstract available.
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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.
Lawrence S Phillips, MD principal investigator
Atlanta VA Medical Center
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, run by Foundation for Atlanta Veterans Education and Research, Inc. 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 7 inclusion and 13 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: status not confirmed, as of the sponsor's last update on 15 Aug 2022. 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?
Results are not available in the source record.
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?
Number of patients who discontinue all pre-meal medications for at least one meal per day (time frame: 24 weeks). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02624908, which also lists 11 linked publications.
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 15 Aug 2022.