Atherosclerosis, Cardiovascular Diseases, Coronary Artery Disease, Endothelial Dysfunction, Sleep Apnea
Conditions
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.
Interventions
DRUGHydroxychloroquine
400mg/daily of hydroxychloroquine for 8 weeks
DRUGPlacebo oral tablet
Amido pills/daily for 8 weeks
Sponsors
Hospital de Clinicas de Porto Alegre
Instituto de Cardiologia do Rio Grande do Sul
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
60 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 fasting glucose blood levels (mg/dL) | before and after eight weeks of treatment with hydroxychloroquine | — |
| 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 |
| 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 glycosylated hemoglobin blood levels (%) | before and after eight weeks of treatment with hydroxychloroquine | — |
Countries
Brazil
Contacts
Primary ContactMaria Claudia Irigoyen
Backup ContactLeticia Maria Silva
Outcome results
None listed