Anti-Inflammatory Drug and Endothelial Function

Coronary Artery Disease Clinical Trial

— HOLD  

Official title:

Effect of Hydroxychloroquine on Endothelial Function: a Clinical Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04161339
• Other study ID #: 5351/17
• Status: Recruiting
• Phase: Phase 4
• Start date: July 1, 2019
• Est. completion date: June 30, 2020

Study information

• Verified date: October 2019
• Source: Instituto de Cardiologia do Rio Grande do Sul
• Contact: Maria Claudia Irigoyen
• Phone: 55 11 985589166
• Email: hipirigoyen[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: June 30, 2020
• Est. primary completion date: June 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Atherosclerosis
• Cardiovascular Diseases
• Coronary Artery Disease
• Endothelial Dysfunction
• Sleep Apnea

Intervention

Drug:
• Hydroxychloroquine
400mg/daily of hydroxychloroquine for 8 weeks
• Placebo oral tablet
Amido pills/daily for 8 weeks

Locations

Country	Name	City	State
Brazil	Hospital de Clinicas de Porto Alegre	Porto Alegre	Rio Grande Do Sul

Sponsors (2)

Lead Sponsor	Collaborator
Instituto de Cardiologia do Rio Grande do Sul	Hospital de Clinicas de Porto Alegre

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Change in fasting glucose blood levels (mg/dL)		before and after eight weeks of treatment with hydroxychloroquine
Secondary	Change in glycosylated hemoglobin blood levels (%)		before and after eight weeks of treatment with hydroxychloroquine
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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