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Genetics of Response to Canagliflozin

NCT ID: NCT02891954

Last Updated: 2025-12-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE1

Total Enrollment

700 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-09-30

Study Completion Date

2026-12-25

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Diabetes Mellitus, Type 2

Keywords

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Glucosuria SGLT2 inhibitors Canagliflozin FGF23 Parathyroid hormone 1,25-Dihydroxyvitamin D Glucagon Ketone bodies Uric acid Pharmacogenomics

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Study Groups

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Single arm

Healthy volunteers will receive canagliflozin to assess pharmacodynamic responses to drug.

Group Type EXPERIMENTAL

Canagliflozin

Intervention Type DRUG

Healthy volunteers will receive canagliflozin (300 mg per day) in the morning for five days.

Interventions

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Canagliflozin

Healthy volunteers will receive canagliflozin (300 mg per day) in the morning for five days.

Intervention Type DRUG

Other Intervention Names

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Invokana (brand name for canagliflozin)

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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

NIH

Sponsor Role collaborator

University of Maryland, Baltimore

OTHER

Sponsor Role lead

Responsible Party

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Simeon I. Taylor

Professor of Medicine

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Simeon I Taylor, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Unversity of Maryland School of Medicine

References

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Taylor SI, Blau JE, Rother KI. Possible adverse effects of SGLT2 inhibitors on bone. Lancet Diabetes Endocrinol. 2015 Jan;3(1):8-10. doi: 10.1016/S2213-8587(14)70227-X. Epub 2014 Dec 16. No abstract available.

Reference Type BACKGROUND
PMID: 25523498 (View on PubMed)

Taylor SI, Blau JE, Rother KI. SGLT2 Inhibitors May Predispose to Ketoacidosis. J Clin Endocrinol Metab. 2015 Aug;100(8):2849-52. doi: 10.1210/jc.2015-1884. Epub 2015 Jun 18.

Reference Type BACKGROUND
PMID: 26086329 (View on PubMed)

Blau JE, Bauman V, Conway EM, Piaggi P, Walter MF, Wright EC, Bernstein S, Courville AB, Collins MT, Rother KI, Taylor SI. Canagliflozin triggers the FGF23/1,25-dihydroxyvitamin D/PTH axis in healthy volunteers in a randomized crossover study. JCI Insight. 2018 Apr 19;3(8):e99123. doi: 10.1172/jci.insight.99123. eCollection 2018 Apr 19.

Reference Type BACKGROUND
PMID: 29669938 (View on PubMed)

Blau JE, Taylor SI. Adverse effects of SGLT2 inhibitors on bone health. Nat Rev Nephrol. 2018 Aug;14(8):473-474. doi: 10.1038/s41581-018-0028-0.

Reference Type BACKGROUND
PMID: 29875481 (View on PubMed)

Beitelshees AL, Leslie BR, Taylor SI. Sodium-Glucose Cotransporter 2 Inhibitors: A Case Study in Translational Research. Diabetes. 2019 Jun;68(6):1109-1120. doi: 10.2337/dbi18-0006.

Reference Type BACKGROUND
PMID: 31109940 (View on PubMed)

Shahidzadeh Yazdi Z, Streeten EA, Whitlatch HB, Montasser ME, Beitelshees AL, Taylor SI. Vitamin D Deficiency Increases Vulnerability to Canagliflozin-induced Adverse Effects on 1,25-Dihydroxyvitamin D and PTH. J Clin Endocrinol Metab. 2024 Jan 18;109(2):e646-e656. doi: 10.1210/clinem/dgad554.

Reference Type RESULT
PMID: 37738423 (View on PubMed)

Shahidzadeh Yazdi Z, Streeten EA, Whitlatch HB, Montasser ME, Beitelshees AL, Taylor SI. Critical Role for 24-Hydroxylation in Homeostatic Regulation of Vitamin D Metabolism. J Clin Endocrinol Metab. 2025 Jan 21;110(2):e443-e455. doi: 10.1210/clinem/dgae156.

Reference Type RESULT
PMID: 38481375 (View on PubMed)

Shahidzadeh Yazdi Z, Streeten EA, Whitlatch HB, Bargal SA, Beitelshees AL, Taylor SI. Value of Vitamin D Metabolite Ratios in 3 Patients as Diagnostic Criteria to Assess Vitamin D Status. JCEM Case Rep. 2024 Jun 28;2(7):luae095. doi: 10.1210/jcemcr/luae095. eCollection 2024 Jul.

Reference Type RESULT
PMID: 38947416 (View on PubMed)

Taylor SI, Cherng HR, Shahidzadeh Yazdi Z, Montasser ME, Whitlatch HB, Mitchell BD, Shuldiner AR, Streeten EA, Beitelshees AL. Pharmacogenetics of sodium-glucose co-transporter-2 inhibitors: Validation of a sex-agnostic pharmacodynamic biomarker. Diabetes Obes Metab. 2023 Dec;25(12):3512-3520. doi: 10.1111/dom.15246. Epub 2023 Aug 22.

Reference Type DERIVED
PMID: 37608471 (View on PubMed)

Other Identifiers

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HP-00069977

Identifier Type: -

Identifier Source: org_study_id

R01DK118942

Identifier Type: NIH

Identifier Source: secondary_id

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