Genetics of Response to Canagliflozin

September 25, 2023 updated by: Simeon I. Taylor, University of Maryland, Baltimore

Pharmacogenomics to Predict Responses to SGLT2 Inhibitors

Five daily doses of canagliflozin (300 mg) will be administered to healthy volunteers. Pharmacodynamic responses to canagliflozin will be assessed both at 2 days and 6 days after administration of the first dose of canagliflozin. A genome-wide association study (GWAS) will be conducted to search for genetic variants that are associated with each of the pharmacodynamic responses to canagliflozin.

Study Overview

Status

Enrolling by invitation

Conditions

Intervention / Treatment

Detailed Description

After obtaining informed consent, healthy Amish research subjects will be screened for eligibility. Immediately after obtaining blood samples for baseline clinical chemistry tests wills, patients will initiate 5 days of canagliflozin (300 mg) treatment. Fasting blood samples will be obtained to assess pharmacodynamic responses at both 48 hours and 120 hours after initiating canagliflozin. The principal pharmacodynamic responses will include 24 hour urinary excretion of glucose, serum chemistries (phosphorus, FGF23, 1,25-dihydroxyvitamin D, parathyroid hormone (PTH), glucagon, beta-hydroxybutyrate, acetoacetate, procollagen type I N-terminal peptide (P1NP), and beta-CTX). Research subjects will undergo genotyping, and a genome-wide association study will be conducted to search for genetic variants that are associated with pharmacodynamic responses to canagliflozin.

Study Type

Interventional

Enrollment (Estimated)

700

Phase

  • Phase 1

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Of Amish descent
  • Age 18 or older
  • BMI: 18-40 kg/m2

Exclusion Criteria:

  • Known allergy to canagliflozin
  • History of diabetes, random glucose greater than 200 mg/dL, or HbA1c greater than or equal to 6.5%
  • Currently taking diuretics, antihypertensive medication uric acid lowering medications, or other medication that the investigator judges will make interpretation of the results difficult
  • Significant debilitating chronic cardiac, hepatic, pulmonary, or renal disease or other diseases that the investigator judges will make interpretation of the results difficult or increase the risk of participation
  • Seizure disorder
  • Unwilling to go off of vitamin supplements and over the counter medication (except for acetaminophen) for at least two weeks prior to the first home visit and agree to avoid these medications for the duration of the study.
  • Positive urine human chorionic gonadotropin test or known pregnancy within 3 months of the start of the study
  • Estimated glomerular filtration rate less than 60 mL/min
  • Currently breast feeding or breast feeding within 3 month of the start of the study
  • Liver function tests greater than 2 times the upper limit of normal
  • Hematocrit less than 35%
  • Abnormal thyroid hormone stimulating hormone

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Single arm
Healthy volunteers will receive canagliflozin to assess pharmacodynamic responses to drug.
Drug: Canagliflozin
Healthy volunteers will receive canagliflozin (300 mg per day) in the morning for five days.
Other Names:
  • Invokana (brand name for canagliflozin)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Urinary glucose excretion (during the time interval 24-48 hours after first administration of canagliflozin)
Time Frame: 24-48 hours
Urine collection will be initiated 24 hours after initiation of canagliflozin treatment, and continued for an additional 24 hours.
24-48 hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Bone-related biomarkers
Time Frame: 48 hrs
Serum phosphorus, FGF23, 1,25-dihydroxyvitamin D, PTH, P1NP, and beta-CTX
48 hrs
Bone-related biomarkers
Time Frame: 120 hrs
Serum phosphorus, FGF23, 1,25-dihydroxyvitamin D, PTH, P1NP, and beta-CTX
120 hrs
Ketosis-related biomarkers
Time Frame: 48 hrs
glucagon, acetoacetate, beta-hydroxybutyrate
48 hrs
Ketosis-related biomarkers
Time Frame: 120 hurs
glucagon, acetoacetate, beta-hydroxybutyrate
120 hurs
Serum uric acid
Time Frame: 48 hrs
Change in serum uric acid at 48 hours
48 hrs
Serum uric acid
Time Frame: 120 hrs
Change in serum uric acid at 120 hours
120 hrs

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Maryland, Baltimore

Collaborators

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

  • Principal Investigator: Simeon I Taylor, MD, PhD, Unversity of Maryland School of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 1, 2016

Primary Completion (Actual)

September 25, 2023

Study Completion (Estimated)

September 25, 2024

Study Registration Dates

First Submitted

August 30, 2016

First Submitted That Met QC Criteria

September 1, 2016

First Posted (Estimated)

September 8, 2016

Study Record Updates

Last Update Posted (Actual)

September 26, 2023

Last Update Submitted That Met QC Criteria

September 25, 2023

Last Verified

September 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HP-00069977
  • R01DK118942 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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