Mechanisms of Weight Loss With SGLT2 Inhibition

• Sponsor: Beth Israel Deaconess Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT02360774
• Collaborator: Janssen Scientific Affairs, LLC (Industry)
• Enrollment: 30
• Location: 1
• Arms: 2
• Duration (Months): 42
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

The purpose of this study is to investigate the effect of canagliflozin, a medication approved by the FDA for the treatment of type 2 diabetes, on body weight and metabolism in people with type 2 diabetes who are overweight or obese.

Canagliflozin lowers glucose levels in the blood by making the kidneys excrete, rather than absorb, glucose. Canagliflozin is also often associated with weight loss.

The study population will generally be type 2 diabetics, ages 18-75 years old, who are overweight or obese.

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes; Overweight; Obesity	Drug: Canagliflozin; Drug: Placebo	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Mechanisms of Weight Loss With SGLT2 Inhibition
• Study Start Date: Feb 1, 2015
• Actual Primary Completion Date: Aug 1, 2018
• Actual Study Completion Date: Aug 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Canagliflozin Subjects will be randomized (1:1) to treatment with canagliflozin 300mg or placebo once daily for 18 weeks.	Drug: Canagliflozin; Subjects will take one 300mg capsule of canagliflozin or identically dispensed placebo by mouth once daily, for 18 weeks.; Other Names: Invokana
Placebo Comparator: Placebo Subjects will be randomized (1:1) to treatment with canagliflozin 300mg or placebo once daily for 18 weeks.	Drug: Placebo; Subjects will take one 300mg capsule of canagliflozin or identically dispensed placebo by mouth once daily, for 18 weeks.

Outcome Measures

Primary Outcome Measures

1. Change in Body Weight [18 weeks (duration of study)]

   Body weight will be measured at each study visit (screening visit, enrollment (study week 0), and at study weeks 2, 4, 8, 12 and 18). Change in body weight will be calculated using ANOVA such that body weight at all time points is included in the data analysis, rather than simply comparing weight at the enrollment visit to weight at the final study visit.

Secondary Outcome Measures

1. Change in Resting Energy Expenditure, Measured Using Indirect Calorimetery [18 weeks (duration of study)]

   Resting energy expenditure will be measured at each study visit using indirect calorimetery. Data analysis will include change in REE from baseline to study conclusion, as well as change in REE throughout the study.

2. Change in Body Composition, Measured Using DXA Scanning. [18 weeks (duration of study)]

   Body composition will be measured at baseline and at study completion using DXA scanning.

3. Change in Glycemic Control [18 weeks (duration of study)]

   Hemoglobin A1C will be measured at baseline and at study completion.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Type 2 diabetes

2. BMI 25-45 kg/m2

3. Hemoglobin A1C > 6.5% but < 9%

4. Normal renal function (GFR > 60)

5. Age 18-75

Exclusion Criteria:

1. Type 1 diabetes

2. History of recurrent UTI or mycotic genital infections

3. Treatment with insulin or a GLP1 agent

4. Pregnant or breastfeeding

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215

Sponsors and Collaborators

• Beth Israel Deaconess Medical Center
• Janssen Scientific Affairs, LLC

Investigators

None specified.

Study Documents (Full-Text)

• Informed Consent Form - Oct 10, 2017
• Study Protocol and Statistical Analysis Plan - Jul 12, 2017

More Information

Publications

None provided.

• Responsible Party: Jody Dushay, Principle Investigator, Beth Israel Deaconess Medical Center
• ClinicalTrials.gov Identifier: NCT02360774
• Other Study ID Numbers: 2014P000335
• First Posted: Feb 11, 2015
• Last Update Posted: Aug 3, 2018
• Last Verified: Aug 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Jody Dushay, Principle Investigator, Beth Israel Deaconess Medical Center: Canagliflozin; Obesity; Weight Loss; Body Weight; Body Weight Changes; Overweight; Sodium-glucose transporter subtype 2 inhibitor
• Additional relevant MeSH terms: Overweight; Weight Loss; Canagliflozin

Study Results

Participant Flow

Arm/Group Title	Canagliflozin	Placebo
Arm/Group Description	Subjects will take one 300mg capsule of canagliflozin once daily for 18 weeks.	Subjects will take one 300mg capsule of identically dispensed placebo by mouth once daily for 18 weeks.
Period Title: Overall Study
STARTED	15	15
COMPLETED	12	13
NOT COMPLETED	3	2

Baseline Characteristics

Arm/Group Title	Placebo	Canagliflozin	Total
Arm/Group Description	Subjects will be randomized (1:1) to treatment with canagliflozin 300mg or placebo once daily for 18 weeks. Placebo: Subjects will take one 300mg capsule of canagliflozin or identically dispensed placebo by mouth once daily, for 18 weeks.	Subjects will be randomized (1:1) to treatment with canagliflozin 300mg or placebo once daily for 18 weeks. Canagliflozin: Subjects will take one 300mg capsule of canagliflozin or identically dispensed placebo by mouth once daily, for 18 weeks.	Total of all reporting groups
Overall Participants	16	15	31
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	12 75%	13 86.7%	25 80.6%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56.6 (1.98)	61.8 (2.9)	59.3 (9.1)
Sex: Female, Male (Count of Participants)
Female	5 31.3%	6 40%	11 35.5%
Male	7 43.8%	7 46.7%	14 45.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 6.3%	1 6.7%	2 6.5%
Not Hispanic or Latino	11 68.8%	12 80%	23 74.2%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	4 25%	7 46.7%	11 35.5%
White	7 43.8%	5 33.3%	12 38.7%
More than one race	1 6.3%	1 6.7%	2 6.5%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	12 75%	13 86.7%	25 80.6%

Outcome Measures

1. Primary Outcome

Title	Change in Body Weight
Description	Body weight will be measured at each study visit (screening visit, enrollment (study week 0), and at study weeks 2, 4, 8, 12 and 18). Change in body weight will be calculated using ANOVA such that body weight at all time points is included in the data analysis, rather than simply comparing weight at the enrollment visit to weight at the final study visit.
Time Frame	18 weeks (duration of study)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Canagliflozin	Placebo
Arm/Group Description	Subjects will take one 300mg capsule of canagliflozin once daily for 18 weeks.	Subjects will take one 300mg capsule of identically dispensed placebo by mouth once daily for 18 weeks.
Measure Participants	13	12
Mean (Standard Error) [kg]	3.0 (0.7)	0.3 (0.9)

2. Secondary Outcome

Title	Change in Resting Energy Expenditure, Measured Using Indirect Calorimetery
Description	Resting energy expenditure will be measured at each study visit using indirect calorimetery. Data analysis will include change in REE from baseline to study conclusion, as well as change in REE throughout the study.
Time Frame	18 weeks (duration of study)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Canagliflozin	Placebo
Arm/Group Description	Subjects will be randomized (1:1) to treatment with canagliflozin 300mg or placebo once daily for 18 weeks. Canagliflozin: Subjects will take one 300mg capsule of canagliflozin or identically dispensed placebo by mouth once daily, for 18 weeks.	Subjects will be randomized (1:1) to treatment with canagliflozin 300mg or placebo once daily for 18 weeks. Placebo: Subjects will take one 300mg capsule of canagliflozin or identically dispensed placebo by mouth once daily, for 18 weeks.
Measure Participants	13	12
Mean (Standard Error) [kcal]	-60.8 (54.4)	-68.6 (84.3)

3. Secondary Outcome

Title	Change in Body Composition, Measured Using DXA Scanning.
Description	Body composition will be measured at baseline and at study completion using DXA scanning.
Time Frame	18 weeks (duration of study)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Canagliflozin	Placebo
Arm/Group Description	Subjects will be randomized (1:1) to treatment with canagliflozin 300mg or placebo once daily for 18 weeks. Canagliflozin: Subjects will take one 300mg capsule of canagliflozin or identically dispensed placebo by mouth once daily, for 18 weeks.	Subjects will be randomized (1:1) to treatment with canagliflozin 300mg or placebo once daily for 18 weeks. Placebo: Subjects will take one 300mg capsule of canagliflozin or identically dispensed placebo by mouth once daily, for 18 weeks.
Measure Participants	13	12
Mean (Standard Error) [% fat]	-0.2 (0.4)	-0.4 (0.4)

4. Secondary Outcome

Title	Change in Glycemic Control
Description	Hemoglobin A1C will be measured at baseline and at study completion.
Time Frame	18 weeks (duration of study)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Canagliflozin	Placebo
Arm/Group Description	Subjects will be randomized (1:1) to treatment with canagliflozin 300mg or placebo once daily for 18 weeks. Canagliflozin: Subjects will take one 300mg capsule of canagliflozin or identically dispensed placebo by mouth once daily, for 18 weeks.	Subjects will be randomized (1:1) to treatment with canagliflozin 300mg or placebo once daily for 18 weeks. Placebo: Subjects will take one 300mg capsule of canagliflozin or identically dispensed placebo by mouth once daily, for 18 weeks.
Measure Participants	13	12
Mean (Standard Error) [percent glycated hemoglobin]	-0.4 (0.1)	-0.1 (0.2)

Adverse Events

Time Frame	duration of the study. each participant was enrolled for up to 18 weeks
Adverse Event Reporting Description	subjects were asked about AEs at each study visit
Arm/Group Title	Placebo		Canagliflozin
Arm/Group Description	Subjects will be randomized (1:1) to treatment with canagliflozin 300mg or placebo once daily for 18 weeks. Placebo: Subjects will take one 300mg capsule of canagliflozin or identically dispensed placebo by mouth once daily, for 18 weeks.		Subjects will be randomized (1:1) to treatment with canagliflozin 300mg or placebo once daily for 18 weeks. Canagliflozin: Subjects will take one 300mg capsule of canagliflozin or identically dispensed placebo by mouth once daily, for 18 weeks.
All Cause Mortality
	Placebo		Canagliflozin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/13 (0%)
Serious Adverse Events
	Placebo		Canagliflozin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/12 (16.7%)		1/13 (7.7%)
Gastrointestinal disorders
abdominal pain	1/12 (8.3%)	1	0/13 (0%)	0
Infections and infestations
pneumonia	0/12 (0%)	0	1/13 (7.7%)	1
infection	1/12 (8.3%)	1	0/13 (0%)	0
Other (Not Including Serious) Adverse Events
	Placebo		Canagliflozin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/12 (41.7%)		5/13 (38.5%)
Endocrine disorders
hypoglycemia	2/12 (16.7%)	2	2/13 (15.4%)	2
Renal and urinary disorders
polyuria	5/12 (41.7%)	5	5/13 (38.5%)	5

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.