CYP4A11 and CYP4F2 Gene Variants as Makers of Cardiovascular Adverse Events of Non-steroidal Anti-inflammatory Drugs

Evaluation of CYP4A11 and CYP4F2 Gene Variants as Makers in Edema and Elevated Blood Pressure Occurrence After Nonsteroidal Anti-inflammatory (NSAID) Use

Randomized, double-blinded, cross-over and placebo controlled clinical trial to evaluate the association between genetic polymorphism of CYP4F2 with cardiovascular adverse effects of non-steroidal anti-inflammatory drugs (NSAIDs). Two groups were included according the CYP4F2 V433M genetic polymorphism (control - MM, N=7 vs. VV or VM variants, N=13). According the sample size planned, a mean difference of total body water delta between groups (control vs. polymorphic) of at least allow 10% could be observed.

Study Overview

• Status: Completed
• Conditions: Drug-Related Side Effects and Adverse Reactions
• Intervention / Treatment: Drug: Diclofenac; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 4

Contacts and Locations

Study Locations

• Brazil
  • Sao Paulo
    • Ribeirao Preto, Sao Paulo, Brazil, 14048900
      • Unidade de Pesquisa Clínica HCRP-USP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria: Healthy volunteers 18-65 years-old -

Exclusion Criteria: Use of drugs and without clinical history of adverse effects of NSAIDS

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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Other: Placebo; Placebo po, b.i.d. for 6 days
Experimental: Diclofenac	Drug: Diclofenac; 50 mg po, b.i.d for 6 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Edema	Presence of edema, measured by the estimative of total body water (deuterium oxide dilution technique). The measurements will be done in the end of 6 days of use of placebo and diclofenac, and the delta between diclofenac and placebo will be used as endpoint	after 6 days of diclofenac and placebo

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood Pressure	Variation (delta) of 24h diastolic blood pressure between placebo and diclofenac phases, measured by ambulatory blood pressure monitoring (ABPM)	after 6 days of diclofenac and placebo

Collaborators and Investigators

• Sponsor: Eduardo Barbosa Coelho

Study record dates

Study Major Dates

• Study Start: October 1, 2011
• Primary Completion (Actual): July 1, 2013
• Study Completion (Actual): July 1, 2013

Study Registration Dates

• First Submitted: May 17, 2016
• First Submitted That Met QC Criteria: May 17, 2016
• First Posted (Estimate): May 20, 2016

Study Record Updates

• Last Update Posted (Estimate): May 20, 2016
• Last Update Submitted That Met QC Criteria: May 17, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Drug-Related Side Effects and Adverse Reactions; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Diclofenac
• Other Study ID Numbers: U1111-1131-8461

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO