Folinic Acid: Supplementation and Therapy

NCT ID: NCT02810275

Last Updated: 2016-11-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 69 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-10-31
• Study Completion Date: 2013-09-30

Brief Summary

Patients infected by HIV or HIV-HCV coinfected have higher survival due to the use of HAART, but survival is accompanied by increased morbidity and associated cardiovascular disease (CVD). Endothelial dysfunction is an early marker of atherogenesis, acting as an intermediate in the causal pathway of CVD. Folinic acid (FA) has been shown to reduce CVD outcomes, especially among individuals with hyperhomocisteinemia.

To date, few studies provided consistent information about efficacy of pharmacological interventions that minimize damage to the vascular endothelium in patients infected by HIV or HIV-HCV coinfected. The main hypothesis of this study is that FA supplementation protects the vascular endothelium, and consequently might prevent subclinical atherosclerosis. Thus, the first step is to determine the efficacy of supplementation with FA, and to compare the effect between HIV and HIV-HCV coinfected.

Detailed Description

Study design: This was a randomized placebo-controlled trial, with blinding of health care team, participants, and investigators, in which the participants were randomly assigned in a 1:1 ratio to receive FA or placebo for four weeks.

Participants: Patients receiving care for HIV, at the outpatient clinic of the Hospital Universitario de Santa Maria, in southern Brazil, from October 2012 to September 2013, were recruited. Eligible participants: HIV infected or HIV-HCV coinfected patients, 18-50 years, men and women, receiving HAART, had undetectable viral load for more than six months. Patients were excluded: patients with diabetes mellitus, previous acute myocardial infarction, myocardial revascularization, or stroke, creatinine >1.5 mg/dL, clinical diagnosis or ultrasound, endoscopic, or laboratory evidence of liver cirrhosis, on treatment with statins, fibrates, hormone replacement therapy, sulfonamides, vitamin supplements, or FA in the last 30 days, and pregnant women.

Intervention Patients assigned to the intervention group received FA 5 mg, per oral, once a day, in the morning, during four weeks. Patients assigned to the placebo group received the same prescription. The trial provided FA and placebo in tablet form, identical in color, smell, taste, shape, and size. Both FA and placebo were prepared in a single batch, in an independent laboratory, by a pharmacist with no involvement in the trial. They were pre-packed in bottles containing 30 tablets each, individually labeled with an alphanumeric code and stored.

Outcomes The primary endpoint were changes in homocysteine, vitamin B12 levels, and brachial artery FMD during reactive hyperemia, as measured by Doppler ultrasound, from randomization to the end of follow-up. FMD was characterized by the variation in mean arterial flow measured as the peak change in vessel diameters relative to the baseline.

Sample size Sample size was calculated based on the results of a previous RCT,(14) which used plethysmography to measure FMD. To detect a difference of at least 6% between intervention and placebo groups, with standard deviations ranging from 5% to 7%, we calculated that a sample size of at least 17 patients per group, with randomization stratified by HCV coinfection status, was required to achieve 80% power and a 95% confidence interval.

Conditions

HIV Infection; HCV Coinfection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

Folinic Acid

Folinic acid group received 5 mg daily during four weeks

Group Type: EXPERIMENTAL

Folinic Acid

Intervention Type: DRUG

Folinic acid 5 mg, taking in the morning, daily, during four weeks

Placebo

Placebo group received a tablet daily during four weeks

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo capsule received 1 tablet, taking in the morning, during four weeks

Interventions

Folinic Acid

Folinic acid 5 mg, taking in the morning, daily, during four weeks

Intervention Type: DRUG

Placebo

Placebo capsule received 1 tablet, taking in the morning, during four weeks

Intervention Type: DRUG

Other Intervention Names

FA; Control

Eligibility Criteria

Inclusion Criteria

• HIV infected patients
• HIV-HCV coinfected patients
• 18-50 years
• men and women
• receiving HAART
• with undetectable viral load for more than six months.

Exclusion Criteria

• Patients with diabetes mellitus,
• previous CVD: acute myocardial infarction, myocardial revascularization, or stroke,
• creatinine >1.5 mg/dL,
• clinical diagnosis or ultrasound, endoscopic, or laboratory evidence of liver cirrhosis,
• on treatment with: statins, fibrates, hormone replacement therapy, sulfonamides, vitamin supplements, or FA in the last 30 days,
• pregnant women.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Universidade Federal de Santa Maria

OTHER

Sponsor Role: collaborator

Hospital de Clinicas de Porto Alegre

OTHER

Sponsor Role: lead

Responsible Party

Sandra Costa Fuchs

Full Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Sandra C Fuchs, PhD, MD

Role: STUDY_CHAIR

Hospital de Clinicas de Porto Alegre

Other Identifiers

GPPG-140240

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

RBR-9366qc

Identifier Type: REGISTRY

Identifier Source: secondary_id

CAAE: 00533612.8.0000.5346

Identifier Type: -

Identifier Source: org_study_id