Anti-Inflammatory Drug and Endothelial Function

Study Overview
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Brief Summary
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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
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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.

Official Title
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Effect of Hydroxychloroquine on Endothelial Function: a Clinical Trial

Conditions
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Cardiovascular Diseases, Endothelial Dysfunction, Sleep Apnea, Atherosclerosis, Coronary Artery Disease

Intervention / Treatment
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* Drug: Hydroxychloroquine
* Drug: Placebo oral tablet


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hydroxychloroquine<br>400mg/daily of hydroxychloroquine for 8 weeks | Drug: Hydroxychloroquine<br>* 400mg/daily of hydroxychloroquine for 8 weeks<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo oral tablet<br>* Amido pills/daily for 8 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in endothelial function measured by peripheral artery tonometry in the reactive-hyperemia index (RHI) scale | 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 | before and after eight weeks of treatment with hydroxychloroquine | 
| Change in endothelial function measured by flow-mediated dilation (%FMD-response) | 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. | before and after eight weeks of treatment with hydroxychloroquine | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | Determined by total cholesterol, HDL-cholesterol and triglycerides blood levels (mg/dL) | before and after eight weeks of treatment with hydroxychloroquine | 
| Change in C-reactive protein (CRP) blood levels (mg/L) | 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 | before and after eight weeks of treatment with hydroxychloroquine | 
| Change in neutrophils lymphocytes ratio (NLR) | 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. | before and after eight weeks of treatment with hydroxychloroquine | 
| Change in Autonomic Nervous System | 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. | before and after eight weeks of treatment with hydroxychloroquine | 
| Change in apnea/hypopnea index | 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 | before and after eight weeks of treatment with hydroxychloroquine |