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Genetics of Response to Canagliflozin

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ClinicalTrials.gov Identifier: NCT02891954
Recruitment Status : Enrolling by invitation
First Posted : September 8, 2016
Last Update Posted : August 12, 2019
Sponsor:
Collaborator:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
Simeon I. Taylor, University of Maryland, Baltimore

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Diabetes Mellitus, Type 2 Drug: Canagliflozin Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 700 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Pharmacogenomics to Predict Responses to SGLT2 Inhibitors
Study Start Date : September 2016
Estimated Primary Completion Date : June 30, 2023
Estimated Study Completion Date : June 30, 2024

Resource links provided by the National Library of Medicine


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 Name: Invokana (brand name for canagliflozin)




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. Bone-related biomarkers [ Time Frame: 48 hrs ]
    Serum phosphorus, FGF23, 1,25-dihydroxyvitamin D, PTH, P1NP, and beta-CTX

  2. Bone-related biomarkers [ Time Frame: 120 hrs ]
    Serum phosphorus, FGF23, 1,25-dihydroxyvitamin D, PTH, P1NP, and beta-CTX

  3. Ketosis-related biomarkers [ Time Frame: 48 hrs ]
    glucagon, acetoacetate, beta-hydroxybutyrate

  4. Ketosis-related biomarkers [ Time Frame: 120 hurs ]
    glucagon, acetoacetate, beta-hydroxybutyrate

  5. Serum uric acid [ Time Frame: 48 hrs ]
    Change in serum uric acid at 48 hours

  6. Serum uric acid [ Time Frame: 120 hrs ]
    Change in serum uric acid at 120 hours



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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

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): NCT02891954


Sponsors and Collaborators
University of Maryland, Baltimore
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
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Principal Investigator: Simeon I Taylor, MD, PhD Unversity of Maryland School of Medicine

Publications:
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Responsible Party: Simeon I. Taylor, Professor of Medicine, University of Maryland, Baltimore
ClinicalTrials.gov Identifier: NCT02891954    
Other Study ID Numbers: HP-00069977
R21DK105401 ( U.S. NIH Grant/Contract )
First Posted: September 8, 2016    Key Record Dates
Last Update Posted: August 12, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Simeon I. Taylor, University of Maryland, Baltimore:
Glucosuria
SGLT2 inhibitors
Canagliflozin
FGF23
Parathyroid hormone
1,25-Dihydroxyvitamin D
Glucagon
Ketone bodies
Uric acid
Pharmacogenomics
Additional relevant MeSH terms:
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Diabetes Mellitus, Type 2
Diabetes Mellitus
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