Autoimmune DiseasesHCQNCT03180190
Genetic Variants in Egyptian Patients Receiving HCQ(Hydroxychloroquine)
An observational study of Autoimmune Diseases, run by Assiut University.
Trial summary
Hydroxychloroquine(HCQ)play major role in management of many rheumatic diseases. Retinal toxicity from HCQ is serious side effect because even after the drug drug is discontinued, there is little if any visual recovery. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Autoimmune Diseases
- What is being tested?
- Hydroxychloroquine Oral Tablet
- Type of treatment
- Pill or oral medicine
- How many people
- 50 participants
- Where
- No sites listed yet
- Study dates
- 28 Jun 2017to 28 Jul 2018
- How long will I take part?
- 1 Year
- Phase
- Observational
- 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 18 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Study population: All patients receiving HCQ treatment
Who may be able to join
- All patients received HCQ treatment and attending the Rheumatology and Rehabilitation outpatient clinic and in-patient department, Faculty of Medicine, Assiut University Hospitals.
Who cannot join
- • Patients less than 18 years old.
- Patients with co-morbidities (e.g., liver disease, serious infections, or cardiac, respiratory, gastrointestinal, endocrine disease) that could influence the disease activity and the liver condition.
- Patients with Renal failure (creatinine clearance < 30 ml/ min).
- Patients with ophthalmic conditions that may give rise to abnormalities in the screening tests used to detect HCQ toxicity e.g. glaucoma, hereditary fundus dystrophies, dense media opacity precluding fundus visibility, optic neuritis and uveitis.
- Patients receiving tamoxifen or other retinal toxin drugs.
About this study
Official title: Cytochrome P450 and ATP-Binding Cassette C C (ABCC) Variants in Egyptian Patients Receiving Hydroxychloroquine and Their Association With Efficacy and Toxicity
Hydroxychloroquine(HCQ)play major role in management of many rheumatic diseases.
Retinal toxicity from HCQ is serious side effect because even after the drug drug is discontinued, there is little if any visual recovery. For this reason, regular screening for retinal toxicity is recommended to detect early retinopathy and discontinue the therapy.
Cytochrome P450 (CYP) enzymes play major roles in drug metabolism. Certain single-nucleotide polymorphisms(SNPs) in CYP genes may have a large impact on CYP enzyme activity.Polymorphisms in the cytochrome P450 gene might influence blood concentration some patients have a genetic predisposition to HCQ toxicity (e.g.,from abnormalities in the ABCA4 gene)Which is not studied previously among Egyptian population
Read the detailed description
The antimalarial agent hydroxychloroquine have been used widely for the treatment of rheumatoid arthritis and systemic lupus erythematosus.
Among rheumatic diseases, the primary role of HCQ is in the management of articular and skin manifestations of systemic lupus erythematosus (SLE) and the treatment of mild to moderately active rheumatoid arthritis (RA). As a cornerstone of SLE management, HCQ leads to reduction in the risk of disease flare as well as providing a valuable adjunct in the therapy of lupus nephritis, and is a relatively safe option for t0reatment of SLE during pregnancy,It also has been linked to the prevention thrombosis as well as a reduced risk of permanent organ damage. HCQ's beneficial effects on lipid levels and reduction in the risk of diabetes .It is a member of the "triple therapy" triad for the treatment of RA , serving as an important component of the therapeutic approach in active disease. Other less common uses for HCQ include the treatment of palindromic rheumatism, Inflammatory cutaneous disorders, and the antiphospholipid antibody syndrome because of its antithrombotic effect .
Retinal toxicity from HCQ is of serious ophthalmologic concern. Because even after the drug is discontinued, there is little if any visual recovery. Additionally, it has been shown that the retinal degeneration caused by HCQ can continue to progress. For this reason, regular screening for retinal toxicity is recommended to detect early retinopathy and discontinue the therapy.
The exact mechanism of HCQ and CQ toxicity remains unclear. Previously, it was hypothesized that retinal toxicity results from binding of HCQ and CQ to melanin in the retinal pigment epithelium (RPE), thus damaging the overlying photoreceptors and ultimately causing vision loss .Whether the primary effect of antimalarials occurs at the level of the RPE versus the retinal photoreceptors has been debated, however, as newer imaging technology has become available ,Early retinal toxicity is generally asymptomatic, with subtle alterations in foveal pigmentation that are often not evident on routine ophthalmologic examination. As toxicity progresses, classic "bull's eye" maculopathy, representing a ring of parafoveal RPE depigmentation sparing the central fovea, may be noted. Progression leads to increasing visual impairment, symptomatically manifesting as decreased central vision, reduced color vision, reduced night vision, reading difficulties, central scotomata, flashing lights, and increasing visual field defects.
Cytochrome P450 (CYP) enzymes play major roles in drug metabolism. Certain single-nucleotide polymorphisms(SNPs) in CYP genes may have a large impact on CYP enzyme activity.Polymorphisms in the cytochrome P450 gene might influence blood concentration.
HCQ is metabolized to N-desethyl HCQ (DHCQ) in the liver through the N-desethylation pathway,This reaction is mediated by CYP 2D6, 3A4, 3A5, and 2C8 isoforms.
some patients have a genetic predisposition to HCQ toxicity (e.g.,from abnormalities in the ABCA4 gene) However, in 2015 ABCA4 polymorphisms proposed that could be protective agent. Which is not studied previously among Egyptian population
- Conditions
- Autoimmune Diseases
- Being tested
- Hydroxychloroquine Oral Tablet
- Medical subject headings
- Autoimmune Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hydroxychloroquine Oral TabletDrug
Also called diagnostic test
slit lamp and fundus examination using both direct and indirect ophthalmoscope Screening for HCQ ocular toxicity by
- Perimetry using Octopus perimeter and utilizing 24-2 test strategy,
- Electroretinography (ERG) under scotopic and photopic conditions and Spectral domain optical coherence tomography (SD-OCT)
| Study group | Role | What they receive |
|---|---|---|
| patients with ocular toxicity | Screening for ophthalmic exclusion criteria by slit lamp and fundus examination using both direct and indirect ophthalmoscope Screening for HCQ ocular toxicity by
* Perimetry using Octopus perimeter and utilizing 24-2 test strategy,
* Electroretinography (ERG) under scotopic and photopic conditions and Spectral domain optical coherence tomography (SD-OCT) genotyping using real time PCR (Taqman discrimination assay) for study frequency of single nucleotide polymorphisms (SNPs) of CYP2C19, CYP1A2, and ABCG2. Receives: Drug: Hydroxychloroquine Oral Tablet | |
| patients without ocular toxicity | Screening for ophthalmic exclusion criteria by slit lamp and fundus examination using both direct and indirect ophthalmoscope Screening for HCQ ocular toxicity by
* Perimetry using Octopus perimeter and utilizing 24-2 test strategy,
* Electroretinography (ERG) under scotopic and photopic conditions and Spectral domain optical coherence tomography (SD-OCT) genotyping using real time PCR (Taqman discrimination assay) for study frequency of single nucleotide polymorphisms (SNPs) of CYP2C19, CYP1A2, and ABCG2. Receives: Drug: Hydroxychloroquine Oral Tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
HCQ toxicity in Egyptian patients
Recognizing clinical and genetic factor(s) affecting the outcome of HCQ therapy in Egyptian patients population and /or predisposing to its toxicity.
Measured: 1 year
Secondary outcomes (1)
genetic variant
Detecting the frequency (distribution) of single nucleotide polymorphisms (SNPs) of CYP and ABCC in Egyptian patients
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jun 2017
- Study start28 Jun 2017 (estimated)
- Primary completion28 Jun 2018 (estimated)
- Study completion28 Jul 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Autoimmune DiseasesStudies of the same condition, open and under way.
- More trials run by Assiut UniversityThe sponsor's other registered studies.
- 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
- Observational
- Observational model
- Case only
- Time perspective
- Cross-sectional
- Enrolment
- 50 participants (estimated)
- Target duration
- 1 Year
Sponsor and investigators
- Lead sponsor
- Assiut University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, nesreen ismail ibrahim, Assiut University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03180190
- Sponsor's protocol ID
- Hydroxychloroquine
- Acronym
- HCQ
- Status last verified
- Jun 2017
- First submitted
- 6 Jun 2017
- Last updated
- 9 Jun 2017
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cytochrome P450 and ATP-Binding Cassette C C (ABCC) Variants in Egyptian Patients Receiving Hydroxychloroquine and Their Association With Efficacy and Toxicity
- ClinicalTrials.gov ID
- NCT03180190
- Acronym / sponsor ID
- HCQ / Hydroxychloroquine
- Conditions
- Autoimmune Diseases
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Assiut UniversityUniversity, hospital or other
- Study start
- 28 Jun 2017 (estimated)
- Primary completion
- 28 Jun 2018 (estimated)
- Study completion
- 28 Jul 2018 (estimated)
- First posted
- 8 Jun 2017 (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.
Hydroxychloroquine(HCQ)play major role in management of many rheumatic diseases.
Retinal toxicity from HCQ is serious side effect because even after the drug drug is discontinued, there is little if any visual recovery. For this reason, regular screening for retinal toxicity is recommended to detect early retinopathy and discontinue the therapy.
Cytochrome P450 (CYP) enzymes play major roles in drug metabolism. Certain single-nucleotide polymorphisms(SNPs) in CYP genes may have a large impact on CYP enzyme activity.Polymorphisms in the cytochrome P450 gene might influence blood concentration some patients have a genetic predisposition to HCQ toxicity (e.g.,from abnormalities in the ABCA4 gene)Which is not studied previously among Egyptian population
Detailed description
The antimalarial agent hydroxychloroquine have been used widely for the treatment of rheumatoid arthritis and systemic lupus erythematosus.
Among rheumatic diseases, the primary role of HCQ is in the management of articular and skin manifestations of systemic lupus erythematosus (SLE) and the treatment of mild to moderately active rheumatoid arthritis (RA). As a cornerstone of SLE management, HCQ leads to reduction in the risk of disease flare as well as providing a valuable adjunct in the therapy of lupus nephritis, and is a relatively safe option for t0reatment of SLE during pregnancy,It also has been linked to the prevention thrombosis as well as a reduced risk of permanent organ damage. HCQ's beneficial effects on lipid levels and reduction in the risk of diabetes .It is a member of the "triple therapy" triad for the treatment of RA , serving as an important component of the therapeutic approach in active disease. Other less common uses for HCQ include the treatment of palindromic rheumatism, Inflammatory cutaneous disorders, and the antiphospholipid antibody syndrome because of its antithrombotic effect .
Retinal toxicity from HCQ is of serious ophthalmologic concern. Because even after the drug is discontinued, there is little if any visual recovery. Additionally, it has been shown that the retinal degeneration caused by HCQ can continue to progress. For this reason, regular screening for retinal toxicity is recommended to detect early retinopathy and discontinue the therapy.
The exact mechanism of HCQ and CQ toxicity remains unclear. Previously, it was hypothesized that retinal toxicity results from binding of HCQ and CQ to melanin in the retinal pigment epithelium (RPE), thus damaging the overlying photoreceptors and ultimately causing vision loss .Whether the primary effect of antimalarials occurs at the level of the RPE versus the retinal photoreceptors has been debated, however, as newer imaging technology has become available ,Early retinal toxicity is generally asymptomatic, with subtle alterations in foveal pigmentation that are often not evident on routine ophthalmologic examination. As toxicity progresses, classic "bull's eye" maculopathy, representing a ring of parafoveal RPE depigmentation sparing the central fovea, may be noted. Progression leads to increasing visual impairment, symptomatically manifesting as decreased central vision, reduced color vision, reduced night vision, reading difficulties, central scotomata, flashing lights, and increasing visual field defects.
Cytochrome P450 (CYP) enzymes play major roles in drug metabolism. Certain single-nucleotide polymorphisms(SNPs) in CYP genes may have a large impact on CYP enzyme activity.Polymorphisms in the cytochrome P450 gene might influence blood concentration.
HCQ is metabolized to N-desethyl HCQ (DHCQ) in the liver through the N-desethylation pathway,This reaction is mediated by CYP 2D6, 3A4, 3A5, and 2C8 isoforms.
some patients have a genetic predisposition to HCQ toxicity (e.g.,from abnormalities in the ABCA4 gene) However, in 2015 ABCA4 polymorphisms proposed that could be protective agent. Which is not studied previously among Egyptian population
Study design
- Observational model
- Case only
- Time perspective
- Cross-sectional
- Target follow-up
- 1 Year
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| patients with ocular toxicity | – | Drug: Hydroxychloroquine Oral TabletScreening for ophthalmic exclusion criteria by slit lamp and fundus examination using both direct and indirect ophthalmoscope Screening for HCQ ocular toxicity by * Perimetry using Octopus perimeter and utilizing 24-2 test strategy, * Electroretinography (ERG) under scotopic and photopic conditions and Spectral domain optical coherence tomography (SD-OCT) genotyping using real time PCR (Taqman discrimination assay) for study frequency of single nucleotide polymorphisms (SNPs) of CYP2C19, CYP1A2, and ABCG2. |
| patients without ocular toxicity | – | Drug: Hydroxychloroquine Oral TabletScreening for ophthalmic exclusion criteria by slit lamp and fundus examination using both direct and indirect ophthalmoscope Screening for HCQ ocular toxicity by * Perimetry using Octopus perimeter and utilizing 24-2 test strategy, * Electroretinography (ERG) under scotopic and photopic conditions and Spectral domain optical coherence tomography (SD-OCT) genotyping using real time PCR (Taqman discrimination assay) for study frequency of single nucleotide polymorphisms (SNPs) of CYP2C19, CYP1A2, and ABCG2. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
- Study population
- All patients receiving HCQ treatment
Key inclusion criteria (1 listed)
- All patients received HCQ treatment and attending the Rheumatology and Rehabilitation outpatient clinic and in-patient department, Faculty of Medicine, Assiut University Hospitals.
Key exclusion criteria (5 listed)
- • Patients less than 18 years old.
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 |
|---|---|---|
| Hydroxychloroquine Oral TabletAlso: diagnostic testslit lamp and fundus examination using both direct and indirect ophthalmoscope Screening for HCQ ocular toxicity by * Perimetry using Octopus perimeter and utilizing 24-2 test strategy, * Electroretinography (ERG) under scotopic and photopic conditions and Spectral domain optical coherence tomography (SD-OCT) | Drug | patients with ocular toxicity, patients without ocular toxicity |
Primary outcome
HCQ toxicity in Egyptian patients
Time frame: 1 year
Recognizing clinical and genetic factor(s) affecting the outcome of HCQ therapy in Egyptian patients population and /or predisposing to its toxicity.
1 secondary outcome
genetic variant
Time frame: 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jun 2017.
- 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.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
An observational study of Autoimmune Diseases, run by Assiut University.
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 5 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 9 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
HCQ toxicity in Egyptian patients (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 9 Jun 2017.