search
Back to results

Canagliflozin-Mealtime Insulin Rescue

Primary Purpose

Diabetes Mellitus, Type 2

Status
Active
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
canagliflozin
placebo
Sponsored by
Foundation for Atlanta Veterans Education and Research, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diabetes Mellitus, Type 2

Eligibility Criteria

30 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  • 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.

Sites / Locations

  • Atlanta VA Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

canagliflozin

placebo

Arm Description

Subjects randomized to this arm will start with 100 mg tablet and increase to 300 mg tablet at Visit 4 if well tolerated.

Subjects randomized to this arm will start with 100 mg tablet and increase to 300 mg tablet at Visit 4 if well tolerated.

Outcomes

Primary Outcome Measures

Number of patients who discontinue all pre-meal medications for at least one meal per day
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
Number of patients with a continuing need for insulin 4 times per day
no change from the original basal -bolus regimen
Frequency and severity of hypoglycemia
Hypoglycemic episodes will be evaluated using a hypoglycemia questionnaire
Self monitoring and continuous monitoring blood glucose levels
glycemic control and glycemic variability

Secondary Outcome Measures

Full Information

First Posted
December 3, 2015
Last Updated
August 12, 2022
Sponsor
Foundation for Atlanta Veterans Education and Research, Inc.
Collaborators
Janssen Scientific Affairs, LLC
search

1. Study Identification

Unique Protocol Identification Number
NCT02624908
Brief Title
Canagliflozin-Mealtime Insulin Rescue
Official Title
Canagliflozin-Mealtime Insulin Rescue
Study Type
Interventional

2. Study Status

Record Verification Date
August 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
January 2016 (Actual)
Primary Completion Date
July 2018 (Actual)
Study Completion Date
December 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Foundation for Atlanta Veterans Education and Research, Inc.
Collaborators
Janssen Scientific Affairs, LLC

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Mellitus, Type 2

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
canagliflozin
Arm Type
Active Comparator
Arm Description
Subjects randomized to this arm will start with 100 mg tablet and increase to 300 mg tablet at Visit 4 if well tolerated.
Arm Title
placebo
Arm Type
Placebo Comparator
Arm Description
Subjects randomized to this arm will start with 100 mg tablet and increase to 300 mg tablet at Visit 4 if well tolerated.
Intervention Type
Drug
Intervention Name(s)
canagliflozin
Other Intervention Name(s)
Invokana
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
placebo
Other Intervention Name(s)
inactive substance
Intervention Description
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.
Primary Outcome Measure Information:
Title
Number of patients who discontinue all pre-meal medications for at least one meal per day
Time Frame
24 weeks
Title
Number of patients who replace mealtime insulin with an oral agent for at least one meal per day
Description
anti-hyperglycemic pill instead of insulin for at least one meal per day
Time Frame
24 weeks
Title
Number of patients with a continuing need for insulin 4 times per day
Description
no change from the original basal -bolus regimen
Time Frame
24 weeks
Title
Frequency and severity of hypoglycemia
Description
Hypoglycemic episodes will be evaluated using a hypoglycemia questionnaire
Time Frame
24 weeks
Title
Self monitoring and continuous monitoring blood glucose levels
Description
glycemic control and glycemic variability
Time Frame
24 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
30 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lawrence S Phillips, MD
Organizational Affiliation
Atlanta VA Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Atlanta VA Medical Center
City
Decatur
State/Province
Georgia
ZIP/Postal Code
30033
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
22686416
Citation
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.
Results Reference
background
PubMed Identifier
18374840
Citation
Bretzel 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. Erratum In: Lancet. 2008 Aug 30;372(9640):718.
Results Reference
background
PubMed Identifier
23564919
Citation
Schernthaner 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. Erratum In: Diabetes Care. 2013 Dec;36(12):4172.
Results Reference
background
PubMed Identifier
23412078
Citation
Polidori 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.
Results Reference
background
PubMed Identifier
22111719
Citation
Budnitz 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.
Results Reference
background
PubMed Identifier
20649629
Citation
Home 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.
Results Reference
background
PubMed Identifier
21421802
Citation
Johnston 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.
Results Reference
background
PubMed Identifier
22992074
Citation
NICE-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.
Results Reference
background
PubMed Identifier
22699297
Citation
McCoy 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.
Results Reference
background
PubMed Identifier
18299315
Citation
Ceriello 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.
Results Reference
background
PubMed Identifier
16609094
Citation
Brownlee 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.
Results Reference
background

Learn more about this trial

Canagliflozin-Mealtime Insulin Rescue

We'll reach out to this number within 24 hrs