Anti-Inflammatory Drug and Endothelial Function (HOLD)
Primary Purpose
Cardiovascular Diseases, Endothelial Dysfunction, Sleep Apnea
Status
Unknown status
Phase
Phase 4
Locations
Brazil
Study Type
Interventional
Intervention
Hydroxychloroquine
Placebo oral tablet
Sponsored by
About this trial
This is an interventional treatment trial for Cardiovascular Diseases
Eligibility Criteria
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
Sites / Locations
- Hospital de Clinicas de Porto AlegreRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Hydroxychloroquine
Placebo
Arm Description
400mg/daily of hydroxychloroquine for 8 weeks
Outcomes
Primary Outcome Measures
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
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.
Secondary Outcome Measures
Change in fasting glucose blood levels (mg/dL)
Change in glycosylated hemoglobin blood levels (%)
Change in Lipidic profile
Determined by total cholesterol, HDL-cholesterol and triglycerides blood levels (mg/dL)
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
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.
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.
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
Full Information
NCT ID
NCT04161339
First Posted
October 29, 2019
Last Updated
November 11, 2019
Sponsor
Instituto de Cardiologia do Rio Grande do Sul
Collaborators
Hospital de Clinicas de Porto Alegre
1. Study Identification
Unique Protocol Identification Number
NCT04161339
Brief Title
Anti-Inflammatory Drug and Endothelial Function
Acronym
HOLD
Official Title
Effect of Hydroxychloroquine on Endothelial Function: a Clinical Trial
Study Type
Interventional
2. Study Status
Record Verification Date
October 2019
Overall Recruitment Status
Unknown status
Study Start Date
July 1, 2019 (Actual)
Primary Completion Date
June 30, 2020 (Anticipated)
Study Completion Date
June 30, 2020 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Instituto de Cardiologia do Rio Grande do Sul
Collaborators
Hospital de Clinicas de Porto Alegre
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cardiovascular Diseases, Endothelial Dysfunction, Sleep Apnea, Atherosclerosis, Coronary Artery Disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
50 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Hydroxychloroquine
Arm Type
Experimental
Arm Description
400mg/daily of hydroxychloroquine for 8 weeks
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Hydroxychloroquine
Intervention Description
400mg/daily of hydroxychloroquine for 8 weeks
Intervention Type
Drug
Intervention Name(s)
Placebo oral tablet
Intervention Description
Amido pills/daily for 8 weeks
Primary Outcome Measure Information:
Title
Change in endothelial function measured by peripheral artery tonometry in the reactive-hyperemia index (RHI) scale
Description
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
Time Frame
before and after eight weeks of treatment with hydroxychloroquine
Title
Change in endothelial function measured by flow-mediated dilation (%FMD-response)
Description
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.
Time Frame
before and after eight weeks of treatment with hydroxychloroquine
Secondary Outcome Measure Information:
Title
Change in fasting glucose blood levels (mg/dL)
Time Frame
before and after eight weeks of treatment with hydroxychloroquine
Title
Change in glycosylated hemoglobin blood levels (%)
Time Frame
before and after eight weeks of treatment with hydroxychloroquine
Title
Change in Lipidic profile
Description
Determined by total cholesterol, HDL-cholesterol and triglycerides blood levels (mg/dL)
Time Frame
before and after eight weeks of treatment with hydroxychloroquine
Title
Change in C-reactive protein (CRP) blood levels (mg/L)
Description
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
Time Frame
before and after eight weeks of treatment with hydroxychloroquine
Title
Change in neutrophils lymphocytes ratio (NLR)
Description
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.
Time Frame
before and after eight weeks of treatment with hydroxychloroquine
Title
Change in Autonomic Nervous System
Description
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.
Time Frame
before and after eight weeks of treatment with hydroxychloroquine
Title
Change in apnea/hypopnea index
Description
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
Time Frame
before and after eight weeks of treatment with hydroxychloroquine
10. Eligibility
Sex
All
Minimum Age & Unit of Time
60 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Maria Claudia Irigoyen
Phone
55 11 985589166
Email
hipirigoyen@gmail.com
First Name & Middle Initial & Last Name or Official Title & Degree
Leticia Maria Silva
Phone
55 51 993220727
Email
tedescosilva.leticia@gmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Denis Martinez
Organizational Affiliation
Federal University of Rio Grande do Sul
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hospital de Clinicas de Porto Alegre
City
Porto Alegre
State/Province
Rio Grande Do Sul
ZIP/Postal Code
90035-007
Country
Brazil
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Andrea Rambo
Phone
+55 51 33598943
First Name & Middle Initial & Last Name & Degree
Eloisa Medeiros
Phone
+55 51 33597604
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
34535165
Citation
Tedesco Silva LM, Cortes A, Rossi B, Boll L, Waclawovsky G, Eibel B, Cadaval Goncalves S, Irigoyen MC, Martinez D. Effects of Hydroxychloroquine on endOthelial function in eLDerly with sleep apnea (HOLD): study protocol for a randomized clinical trial. Trials. 2021 Sep 17;22(1):638. doi: 10.1186/s13063-021-05610-0. Erratum In: Trials. 2021 Oct 18;22(1):709.
Results Reference
derived
Learn more about this trial
Anti-Inflammatory Drug and Endothelial Function
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