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Role of Canagliflozin on CD34+ Cells in Patients With Type 2 Diabetes

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ClinicalTrials.gov Identifier: NCT02964585
Recruitment Status : Recruiting
First Posted : November 16, 2016
Last Update Posted : February 5, 2019
Sponsor:
Collaborator:
Janssen Scientific Affairs, LLC
Information provided by (Responsible Party):
Sabyasachi Sen, George Washington University

Brief Summary:

The investigators hypothesize that Cana may be able to improve number and function of CD34+ endothelial progenitor cells. The investigators also propose that this expected cardiovascular benefit is independent of HbA1C reduction.

Subjects will begin taking 100 mg of Cana or placebo after initial 4 weeks. Subjects will be withdrawn from the study if the medication or placebo is not tolerated.


Condition or disease Intervention/treatment Phase
Type 2 Diabetes Mellitus Drug: Canagliflozin Drug: Placebo Phase 4

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Role of Canagliflozin on Gene Expression and Function of CD34+ Endothelial Progenitor Cells and Renal Function in Patients With Type 2 Diabetes
Actual Study Start Date : November 2016
Estimated Primary Completion Date : September 2019
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Active Arm
100 mg of Canagliflozin for 16 weeks
Drug: Canagliflozin
100 mg
Other Name: INVOKANA

Placebo Comparator: Placebo Arm
Placebo for 16 weeks
Drug: Placebo
1 tablet daily for 16 weeks




Primary Outcome Measures :
  1. Gene Expression and Function change of CD34+ Endothelial Progenitor Cells [ Time Frame: Up to 12 weeks post Canagliflozin treatment ]
    To determine whether 4 months of Canagliflozin modifies CD34+ cell number, gene expression and migration function. The investigators will obtain a total of approximately 95 mL of peripheral blood per visit. Of these 95 mL, 60-70 mL will be used to obtain CD34+ cells from mononuclear cell (MNC) population and 25-35 mL for biochemistry and plasma ELISA assays. MNC will be obtained from whole blood similar to protocols described before [13,14]. MNCs will be put through CD34 magnetic bead column to obtain CD34+ cells (Miltenyi Biotec). Purity of CD34+ cells, post sort, usually is above 90%, to be verified by FACS analysis.


Secondary Outcome Measures :
  1. Serum Endothelial Inflammatory Markers [ Time Frame: Up to 8 and 16 weeks post Canagliflozin treatment ]
    Highly selective C-reactive protein (hs-CRP), IL-6, and TNF-alpha

  2. Fasting Lipid Profile [ Time Frame: Up to 8 and 16 weeks post Canagliflozin treatment ]
    Measured from a serum blood Lipid Panel

  3. Glycemic Control [ Time Frame: Up to 8 and 16 weeks post Canagliflozin treatment ]
    Measured from blood glucose and HbA1C values

  4. Creatinine Clearance [ Time Frame: Up to 8 and 16 weeks post Canagliflozin treatment ]
    Measured from compiled results from a urine sample and blood tests

  5. Adiposity [ Time Frame: Up to 8 and 16 weeks post Canagliflozin treatment ]
    Measured using a body composition scale

  6. Resting Metabolic Rate (RMR) [ Time Frame: Up to 8 and 16 weeks post Canagliflozin treatment ]
    Using ReeVue (trademark) machine, with or without SGLT2 inhibitor therapy to ascertain if Cana has any effect on RMR. Other related trials have shown weight loss but effect on metabolic rate has not been studied .

  7. Vessel Health [ Time Frame: Up to 8 and 16 weeks post Canagliflozin treatment ]
    Vessel health will be assessed by using arterial tonometry with the SphygmoCor CP system from ATCOR .



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Ages Eligible for Study:   30 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age 30-70 years
  • Currently treated with any combination of the following anti-diabetic therapies: metformin (1-2 grams), insulin, GLP-1 agonists, a DPP-IV inhibitor, or sulfonylureas
  • Hemoglobin A1C (HbA1C) between 7.0% and 10.0%
  • Body Mass Index (BMI) between 25 and 39.9 kg/m^2 (both inclusive)

Exclusion Criteria:

  • Type 1 diabetes
  • History of hyperosmolar nonketotic coma
  • History of diabetic ketoacidosis in the last 3 months
  • Abnormal CBC that is judged by physician to be unsafe to enroll or low hematocrit (<28 UNITS).
  • History of pancreatitis
  • History of diabetic ketoacidosis in the last 3 months
  • History of cancer (except basal cell carcinoma and cancer that is cured or not active or being treated in the past 5 years)
  • Heart attack or stroke within 6 months of screening
  • Clinically significant coronary and/or peripheral vascular disease that would be unsafe to enroll in the study.
  • Statin use started or dose change in the last 3 months
  • CKD Stages 3,4 and 5
  • Use of oral or injectable anti-diabetic medication other than any combination of the following anti-diabetic therapies: metformin (1-2 grams), insulin, GLP-1 agonists, a DPP-IV inhibitor, or sulfonylureas currently, or in the past 1 month.
  • Use of consistent long-term steroid medication (oral, inhaled, injected) within the last 3 months
  • Uncontrolled inflammatory disease, or current chronic use of anti-inflammatory drugs within the last 3 months. **This will be judged on a case by case basis by the PI**
  • Implanted devices (e.g., pacemakers) that may interact with Body Composition scale
  • Untreated Systolic Blood Pressure > 150 mmHg and diastolic Blood Pressure > 90 mmHg
  • Active wounds or recent surgery within 3 months
  • Untreated hyper/hypothyroidism

Physical and Laboratory Test Findings:

  • Pre-existing liver disease and/or ALT and AST >2.5X's UNL
  • Serum creatinine levels ≥2.0
  • Estimated CrCl < 60 mL/min (measured by eGFR value)
  • Triglycerides >450 mg/dL

Allergies and Adverse Drug Reactions:

  • Subjects with a history of any serious hypersensitivity reaction to Cana or another SGLT2 inhibitor.

Sex and Reproductive Status:

  • Women in reproductive age group will be included in the study but encouraged to use contraceptive method to avoid pregnancy within 16 weeks of study duration.
  • Women who are pregnant or breast-feeding will be excluded.

Other Exclusion Criteria:

  • Prisoners or subjects who are involuntarily incarcerated.
  • Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness.
  • Patients who are active smokers
  • Patients who are pregnant
  • Nursing women
  • Post-menopausal women who are on estrogen hormone replacement therapy will be excluded.
  • Patients on low dose oral contraceptives will be allowed to participate as these formulations contain very low amounts of estrogens.
  • Eligibility criteria for this study have been carefully considered to ensure the safety of the study subjects and to ensure that the results of the study can be used. It is imperative that subjects fully meet all eligibility criteria.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02964585


Contacts
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Contact: Hassan Awal 202-741-2389 hawal@mfa.gwu.edu

Locations
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United States, District of Columbia
The George Washington University Medical Faculty Associates Recruiting
Washington, District of Columbia, United States, 20037
Contact: Hassan Awal    202-741-2389    hawal@mfa.gwu.edu   
Sponsors and Collaborators
George Washington University
Janssen Scientific Affairs, LLC
Investigators
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Principal Investigator: Sabyasachi Sen, MD, PhD Medical Faculty Associates

Publications of Results:
Sabyasachi Sen, Sarah Witkowski, Ann Lagoy, Ashequl M. Islam: A six-week home exercise program improves endothelial function and CD34+ circulating progenitor cells in patients with pre-diabetes. J Endocrinol Metab.2015; 5 (1-2):163-171, doi: http://dx.doi.org/10.14740/jem273w.

Other Publications:
Department of Health and Human Services, NIH and National Center for Chronic Disease Prevention and Health Promotion, "National Diabetes Statistics: 2007 and 2011 Fact Sheet." 2011

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Responsible Party: Sabyasachi Sen, Associate Professor of Medicine, George Washington University
ClinicalTrials.gov Identifier: NCT02964585     History of Changes
Other Study ID Numbers: GW-CANA-081635
First Posted: November 16, 2016    Key Record Dates
Last Update Posted: February 5, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Sabyasachi Sen, George Washington University:
Type 2 Diabetes Mellitus
Endothelial Cells
Cellular Biomarker
Endothelial Dysfunction
CD34+
Impaired renal function

Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Canagliflozin
Sodium-Glucose Transporter 2 Inhibitors
Molecular Mechanisms of Pharmacological Action
Hypoglycemic Agents
Physiological Effects of Drugs