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Effects of Canagliflozin on Intravascular Volume and Hemodynamics

Primary Purpose

Type2 Diabetes Mellitus, Cardiovascular Diseases

Status

Withdrawn

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

Canagliflozin 300mg

Placebo

About this trial

This is an interventional basic science trial for Type2 Diabetes Mellitus

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

on stable doses (more than 3 months) of antihyperglycemic agents (except for an SGLT2 inhibitor and insulin)
have an A1c ≥7% and ≤11%
Estimated glomerular filtration rate (eGFR) must be ≥45 ml/min•1.73 m2
have an NT-proBNP ≥500 pg/mL
be on a stable dose of guideline-directed HF medication (i.e., angiotensin converting enzyme [ACE] inhibitor, angiotensin II receptor blocker [ARB], or angiotensin receptor neprilysin inhibitor [ARNI], β-blocker, diuretics, and/or mineralcorticoid receptor antagonist) for at least 4 weeks
be on stable antihypertensive therapy for at least 2 months

Exclusion Criteria:

T1DM
repeated fasting plasma glucose (FPG) or fasting self-monitored blood glucose measurements ≥240 mg/dL or both
during the pretreatment phase, NYHA Class IV HF status, uncontrolled hypertension as defined as systolic blood pressure (SBP) >160 or diastolic blood pressure (DBP) >100 mmHg
liver disease (ALT or AST >3 x ULN)
anemia Hb<10
anticipated cardiac surgery or coronary intervention within the next 3 months
severe unremediated valvular heart disease
major CV event (e.g., MI, cerebrovascular accident) within 3 months prior to screening visit
hospitalization for HF within 2 months prior to screening visit
documented atrial fibrillation
history of atraumatic amputation within past 12 months of screening or critical ischemia of the lower extremity within 6 months of screening
an active skin ulcer, osteomyelitis, or gangrene
have an allergy to iodocyanine green and inulin

Sites / Locations

The University of Texas Health Science Center at San Antonio

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Canagliflozin Group

Placebo Group

Arm Description

Assuming a 25% dropout rate, 16 individuals in the canagliflozin group

Assuming a 25% dropout rate, 11 individuals in the placebo group

Outcomes

Primary Outcome Measures

Change in Pulmonary capillary wedge pressure (PCWP)

The primary efficacy endpoint will be change in PCWP from baseline to end of acute administration monitoring period (6 hours).

Secondary Outcome Measures

Change in Pulmonary capillary wedge pressure (PCWP)

The key secondary endpoint will be change in PCWP from baseline to 4 weeks.

Full Information

NCT ID

NCT03190798

First Posted

June 15, 2017

Last Updated

October 10, 2017

Sponsor

The University of Texas Health Science Center at San Antonio

Collaborators

Janssen Scientific Affairs, LLC

1. Study Identification

Unique Protocol Identification Number

NCT03190798

Brief Title

Effects of Canagliflozin on Intravascular Volume and Hemodynamics

Official Title

A Randomized, Double-Blind, Placebo-Controlled, Single-Center, Mechanistic Study to Evaluate the Effects of Canagliflozin on Intravascular Volume and Hemodynamics in Subjects With Type 2 Diabetes Mellitus and Heart Failure

Study Type

Interventional

2. Study Status

Record Verification Date

July 2017

Overall Recruitment Status

Withdrawn

Why Stopped

Study has been withdrawn from IRB review pending IND revision

Study Start Date

September 1, 2017 (Anticipated)

Primary Completion Date

August 1, 2018 (Anticipated)

Study Completion Date

August 1, 2018 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

The University of Texas Health Science Center at San Antonio

Collaborators

Janssen Scientific Affairs, LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

RESEARCH HYPOTHESIS In subjects with T2DM and HF, effect of canagliflozin will be superior to placebo for the change from baseline in PCWP after a single dose (6 hours post-dose) and after 4 weeks. Treatment with canagliflozin will be well tolerated over 4 weeks.

Detailed Description

This is a randomized, double-blind, placebo-controlled, parallel-group, single-center study (Figure 1). Thirty subjects will be randomized in a 3:2 randomization ratio to canagliflozin 300 mg once daily (QD) or placebo. The study will include a 3-week pretreatment screening phase and a 4-week double-blind treatment phase.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Type2 Diabetes Mellitus, Cardiovascular Diseases

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Model Description

Randomized, Double-Blind, Placebo-Controlled, Single-Center, Mechanistic Study

Masking

ParticipantCare Provider

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Canagliflozin Group

Arm Type

Active Comparator

Arm Description

Assuming a 25% dropout rate, 16 individuals in the canagliflozin group

Arm Title

Placebo Group

Arm Type

Placebo Comparator

Arm Description

Assuming a 25% dropout rate, 11 individuals in the placebo group

Intervention Type

Drug

Intervention Name(s)

Canagliflozin 300mg

Other Intervention Name(s)

Invokana

Intervention Description

Canagliflozin is a sodium-glucose cotransporter 2 (SGLT2) inhibitor. It works by decreasing the amount of sugar the body absorbs, and increasing the amount of sugar that leaves the body in the urine. Administered in 300mg tablets.

Intervention Type

Drug

Intervention Name(s)

Placebo

Other Intervention Name(s)

Canagliflozin Placebo

Intervention Description

Placebo for Canagliflozin

Primary Outcome Measure Information:

Title

Change in Pulmonary capillary wedge pressure (PCWP)

Description

The primary efficacy endpoint will be change in PCWP from baseline to end of acute administration monitoring period (6 hours).

Time Frame

6 hours

Secondary Outcome Measure Information:

Title

Change in Pulmonary capillary wedge pressure (PCWP)

Description

The key secondary endpoint will be change in PCWP from baseline to 4 weeks.

Time Frame

4 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: on stable doses (more than 3 months) of antihyperglycemic agents (except for an SGLT2 inhibitor and insulin) have an A1c ≥7% and ≤11% Estimated glomerular filtration rate (eGFR) must be ≥45 ml/min•1.73 m2 have an NT-proBNP ≥500 pg/mL be on a stable dose of guideline-directed HF medication (i.e., angiotensin converting enzyme [ACE] inhibitor, angiotensin II receptor blocker [ARB], or angiotensin receptor neprilysin inhibitor [ARNI], β-blocker, diuretics, and/or mineralcorticoid receptor antagonist) for at least 4 weeks be on stable antihypertensive therapy for at least 2 months Exclusion Criteria: T1DM repeated fasting plasma glucose (FPG) or fasting self-monitored blood glucose measurements ≥240 mg/dL or both during the pretreatment phase, NYHA Class IV HF status, uncontrolled hypertension as defined as systolic blood pressure (SBP) >160 or diastolic blood pressure (DBP) >100 mmHg liver disease (ALT or AST >3 x ULN) anemia Hb<10 anticipated cardiac surgery or coronary intervention within the next 3 months severe unremediated valvular heart disease major CV event (e.g., MI, cerebrovascular accident) within 3 months prior to screening visit hospitalization for HF within 2 months prior to screening visit documented atrial fibrillation history of atraumatic amputation within past 12 months of screening or critical ischemia of the lower extremity within 6 months of screening an active skin ulcer, osteomyelitis, or gangrene have an allergy to iodocyanine green and inulin

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Devjit Tripathy, MD

Organizational Affiliation

The University of Texas Health Science Center at San Antonio

Official's Role

Principal Investigator

Facility Information:

Facility Name

The University of Texas Health Science Center at San Antonio

City

San Antonio

State/Province

Texas

ZIP/Postal Code

78229

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

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Effects of Canagliflozin on Intravascular Volume and Hemodynamics

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