Anti-Inflammatory Drug and Endothelial Function

Phase 4

• Conditions: Coronary Artery Disease; Cardiovascular Diseases; Endothelial Dysfunction; Atherosclerosis; Sleep Apnea
• Interventions: Drug: Hydroxychloroquine; Drug: Placebo oral tablet

• Registration Number: NCT04161339
• Lead Sponsor: Instituto de Cardiologia do Rio Grande do Sul

Brief Summary

In this randomized double-blinded clinical trial, 400mg of hydroxychloroquine will be given daily to people over the age of 65 years with moderate-severe obstructive sleep apnea for 8 weeks. The aim of this study is to test whether hydroxychloroquine can improve endothelial function.

Detailed Description

Sleep apnea and coronary artery disease are prevalent and relevant diseases due to their morbidity and mortality. The mechanism by which sleep apnea leads to coronary artery disease remains unclear. It is known that intermittent hypoxia, the main characteristic of sleep apnea, leads to inflammation and consequently may lead to endothelial dysfunction. Endothelial dysfunction precedes the development of atherosclerotic disease and the occurrence of cardiovascular events. Agents that potentially act to improve endothelial function may assist in the prevention of cardiovascular events. Patients using immunomodulators due to rheumatic diseases have a lower prevalence of cardiovascular diseases. However, the cardioprotective effect of these drugs in patients without autoimmune diseases is not known. Hydroxychloroquine (HCQ) is an immunomodulator used in the treatment of rheumatoid arthritis and systemic lupus erythematosus. In addition to its anti-inflammatory properties, HCQ reduces cholesterol and glycemia levels and has antithrombotic effects. The drug is inexpensive and widely available. The adverse effects of HCQ are rare and occur more frequently when using high doses.

Study Timeline

• Study Start: 2019-07-01
• Status Verified: 2019-10
• Study First Submitted: 2019-10-29
• Study First Submitted QC: 2019-11-11
• Last Update Submitted: 2019-11-11
• Study First Posted: 2019-11-13
• Last Update Posted: 2019-11-13
• Primary Completion: 2020-06-30
• Study Completion: 2020-06-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

• Apnea-Hypopnea index of 15 events/hour or higher

Exclusion Criteria

• Contraindication for hydroxychloroquine (retinopathy, chronic liver disease, chronic renal disease)
• Rheumatologic disease

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Hydroxychloroquine	Hydroxychloroquine	400mg/daily of hydroxychloroquine for 8 weeks
Placebo	Placebo oral tablet	-

Primary Outcome Measures

Name	Time	Method
Change in endothelial function measured by flow-mediated dilation (%FMD-response)	before and after eight weeks of treatment with hydroxychloroquine	The FMD-response will be calculated as the variation in post-hyperaemia brachial artery diameter from baseline, measured in relative (percentage) change. A mean improvement in flow mediated dilatation of at least 2% would usually be required to detect a treatment benefit.
Change in endothelial function measured by peripheral artery tonometry in the reactive-hyperemia index (RHI) scale	before and after eight weeks of treatment with hydroxychloroquine	The reactive-hyperemia index (RHI) scale ranges from -0.4 to 1.6. Below -0.51 being endothelial dysfunction, a higher score indicates a better endothelial function

Secondary Outcome Measures

Name	Time	Method
Change in fasting glucose blood levels (mg/dL)	before and after eight weeks of treatment with hydroxychloroquine
Change in glycosylated hemoglobin blood levels (%)	before and after eight weeks of treatment with hydroxychloroquine
Change in Lipidic profile	before and after eight weeks of treatment with hydroxychloroquine	Determined by total cholesterol, HDL-cholesterol and triglycerides blood levels (mg/dL)
Change in C-reactive protein (CRP) blood levels (mg/L)	before and after eight weeks of treatment with hydroxychloroquine	The risk of developing cardiovascular disease is quantified as follows: low: CRP level under 1.0 mg/L average: between 1.0 and 3.0 mg/L high: above 3.0 mg/L
Change in neutrophils lymphocytes ratio (NLR)	before and after eight weeks of treatment with hydroxychloroquine	calculated by dividing the number of neutrophils by number of lymphocytes. The mean range of healthy adult subjects is between 0.78 and 3.53.
Change in Autonomic Nervous System	before and after eight weeks of treatment with hydroxychloroquine	The data will be collected through the system of acquisition of pressure waves in a continuous and non-invasive way by the Finometer® system, through a cuffing installed in the middle finger, taking this signal to an analog-to-digital signal converter. The pulse pressure signal will be acquired at 1000 Hz, continuously and non-invasively, supine (10 minutes) in a quiet environment, with controlled temperature (± 23 ° C) and illumination. The collected data will be saved in the software BeatsScope® and LabChart®, from which will be extracted the systograms for analysis.
Change in apnea/hypopnea index	before and after eight weeks of treatment with hydroxychloroquine	Apnea/Hypopnea index is provided by home respiratory polygraphy, ranging from 0-highest events/hour, zero-5 eventos/hour being normal and above 5 events/hour being abnormal

Trial Locations

Locations (1)

Hospital de Clinicas de Porto Alegre; 🇧🇷 Porto Alegre, Rio Grande Do Sul, Brazil