Pharmacogenetics of SGLT2 Inhibitors

Sponsor
University of Maryland, Baltimore
Study ID
NCT02462421
Phase
PHASE4
Status
Terminated

Conditions

Eligibility Criteria

Sex
ALL
Age
21 Years - N/A
Healthy Volunteers
Accepted

Interventions

  • Canagliflozin — DRUG
    A single dose of canagliflozin (300 mg, p.o.) will be administered prior to assessing pharmacodynamic response.

Study Details

Sodium-dependent glucose transporter-2 (SGLT2) inhibitors are a new class of anti-diabetic drugs, which increase urinary glucose excretion thereby promoting weight loss and decreasing plasma glucose levels. We hypothesize that the pharmacodynamic response to SGLT2 inhibitors (specifically canagliflozin) varies among individuals, and that a proportion of this inter-individual variation can be explained by genetic variation. This is a pilot study in healthy, non-diabetic subjects in whom glucose and other related metabolites in the urine and plasma will be measured before and after administration of a single dose of canagliflozin. This will allow us to characterize the inter-individual variation in the pharmacodynamic response to canagliflozin as well as determine if changes in glucose and other related metabolite levels are associated with variants in various candidate genes.

Key Dates

Start date
Jun 1, 2015
Status verified
Jul 2022
Primary completion
Dec 31, 2021
Completion
Dec 31, 2021

Study Design

Enrollment
30 participants (actual)
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE

Arms

  • Active Comparator: Wild type genotype
    Research subjects with wild type genotypes at three candidate genes encoding sodium-dependent glucose transporter-3, sodium-dependent glucose transporter-4, and glucose transporter-9 (abbreviated as SLC5A4, SLC5A9, SLC2A9, respectively) will be studied before and after canagliflozin treatment.
  • Experimental: Nonsense mutation in SLC5A4
    Research subjects who are homozygous for nonsense mutation in SLC5A4 (sodium-dependent glucose transporter-3) will be studied before and after canagliflozin treatment.
  • Experimental: Nonsense mutation in SLC5A9
    Research subjects who are homozygous for nonsense mutation in SLC5A9 (sodium-dependent glucose transporter-4) will be studied before and after canagliflozin treatment.
  • Experimental: Missense variant in SLC2A9
    Research subjects who are homozygous for nonsynonymous variant in glucose transporter-9 (SLC2A9) will be studied before and after canagliflozin treatment.

Primary Outcome Measure

Urinary Excretion of Glucose (Measured During the 24 Hours Following Administration of Canagliflozin) [ Time Frame: 24 hours after administration of canagliflozin ]

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