Cardiovascular DiseasesPhase 4HOLDNCT04161339
Anti-Inflammatory Drug and Endothelial Function
A Phase 4 study testing Hydroxychloroquine in people with Cardiovascular Diseases and Endothelial Dysfunction, run by Instituto de Cardiologia do Rio Grande do Sul at 1 site in Brazil.
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. Read more about this study
- Who is it for?
- Ages 60 to 80 years
- Conditions the study is for
- Cardiovascular Diseases, Endothelial Dysfunction, Sleep Apnea
- What is being tested?
- Hydroxychloroquine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 1 siteBrazil
- Study dates
- 1 Jul 2019to 30 Jun 2020
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 60 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Apnea-Hypopnea index of 15 events/hour or higher
Who cannot join
- Contraindication for hydroxychloroquine (retinopathy, chronic liver disease, chronic renal disease)
- Rheumatologic disease
Trial locations and contacts
1 site in 1 country.
Brazil1 site, 1 recruiting
- Recruiting
Hospital de Clinicas de Porto Alegre
Porto Alegre, Rio Grande do Sul, 90035-007
Andrea Rambo, +55 51 33598943
Eloisa Medeiros, +55 51 33597604
About this study
Official title: Effect of Hydroxychloroquine on Endothelial Function: a Clinical Trial
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.
Read the 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.
- Conditions
- Cardiovascular Diseases, Endothelial Dysfunction, Sleep Apnea, Atherosclerosis, Coronary Artery Disease
- Being tested
- Hydroxychloroquine, Placebo oral tablet
- Medical subject headings
- Cardiovascular Diseases, Sleep Apnea Syndromes, Atherosclerosis, Coronary Artery Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
400mg/daily of hydroxychloroquine for 8 weeks
Placebo oral tabletDrug
Amido pills/daily for 8 weeks
| Study group | Role | What they receive |
|---|---|---|
| Hydroxychloroquine | Experimental | 400mg/daily of hydroxychloroquine for 8 weeks Receives: Drug: Hydroxychloroquine |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo oral tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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.
Measured: before and after eight weeks of treatment with hydroxychloroquine
Secondary outcomes (7)
Change in fasting glucose blood levels (mg/dL)
Measured: before and after eight weeks of treatment with hydroxychloroquine
Change in glycosylated hemoglobin blood levels (%)
Measured: 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)
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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
Measured: before and after eight weeks of treatment with hydroxychloroquine
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Nov 2019
- Study start1 Jul 2019
- Primary completion30 Jun 2020 (estimated)
- Study completion30 Jun 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cardiovascular DiseasesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Instituto de Cardiologia do Rio Grande do Sul
- Sponsor type
- University, hospital or other
- Collaborators
- Hospital de Clinicas de Porto Alegre
- Responsible party
- Sponsor
- Investigators
- Denis Martinez, Principal investigator, Federal University of Rio Grande do Sul
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04161339
- Sponsor's protocol ID
- 5351/17
- Acronym
- HOLD
- Status last verified
- Oct 2019
- First submitted
- 29 Oct 2019
- Last updated
- 13 Nov 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 34535165
Study at a glance
From the registry record, last updated by the sponsor on 13 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Hydroxychloroquine on Endothelial Function: a Clinical Trial
- ClinicalTrials.gov ID
- NCT04161339
- Acronym / sponsor ID
- HOLD / 5351/17
- Conditions
- Cardiovascular Diseases, Endothelial Dysfunction, Sleep Apnea, Atherosclerosis, Coronary Artery Disease
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Instituto de Cardiologia do Rio Grande do SulUniversity, hospital or other
- Collaborators
- Hospital de Clinicas de Porto Alegre
- Study start
- 1 Jul 2019 (actual)
- Primary completion
- 30 Jun 2020 (estimated)
- Study completion
- 30 Jun 2020 (estimated)
- First posted
- 13 Nov 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Hydroxychloroquine | Experimental | Drug: Hydroxychloroquine400mg/daily of hydroxychloroquine for 8 weeks |
| Placebo | Placebo comparator | Drug: Placebo oral tablet |
Who may qualify
- Ages
- 60 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Apnea-Hypopnea index of 15 events/hour or higher
Key exclusion criteria (2 listed)
- Contraindication for hydroxychloroquine (retinopathy, chronic liver disease, chronic renal disease)
- Rheumatologic disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Hydroxychloroquine400mg/daily of hydroxychloroquine for 8 weeks | Drug | Hydroxychloroquine |
| Placebo oral tabletAmido pills/daily for 8 weeks | Drug | Placebo |
Primary outcome
Change in endothelial function measured by peripheral artery tonometry in the reactive-hyperemia index (RHI) scale
Time frame: 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)
Time frame: 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.
7 secondary outcomes
Change in fasting glucose blood levels (mg/dL)
Time frame: before and after eight weeks of treatment with hydroxychloroquine
Change in glycosylated hemoglobin blood levels (%)
Time frame: before and after eight weeks of treatment with hydroxychloroquine
Change in Lipidic profile
Time frame: before and after eight weeks of treatment with hydroxychloroquine
Change in C-reactive protein (CRP) blood levels (mg/L)
Time frame: before and after eight weeks of treatment with hydroxychloroquine
Change in neutrophils lymphocytes ratio (NLR)
Time frame: before and after eight weeks of treatment with hydroxychloroquine
Change in Autonomic Nervous System
Time frame: before and after eight weeks of treatment with hydroxychloroquine
Change in apnea/hypopnea index
Time frame: before and after eight weeks of treatment with hydroxychloroquine
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Nov 2019.
- Derived from this study: PubMed 34535165Tedesco 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Denis Martinez principal investigator
Federal University of Rio Grande do Sul
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Hydroxychloroquine in people with Cardiovascular Diseases and Endothelial Dysfunction, run by Instituto de Cardiologia do Rio Grande do Sul at 1 site in Brazil.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 13 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Maria Claudia Irigoyen (55 11 985589166, hipirigoyen@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in endothelial function measured by peripheral artery tonometry in the reactive-hyperemia index (RHI) scale (time frame: before and after eight weeks of treatment with hydroxychloroquine). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04161339, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Nov 2019.