Proportion of Clinical Improvement & Type 1 Interferon (IFN) Score Changes in Idiopathic Uveitis Patients With Interferon Gamma Release Assay (IGRA) Positive

NCT04088019 | Recruiting

• 1 other identifier: 19-06-0769
• Study Type: observational
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this study is to determine the proportion of clinical improvement, the score changing of type 1 interferon selected gene expression, and analysis of transcriptomics profiling in patients with idiopathic uveitis positive IGRA before and after receiving Anti-Tuberculosis Therapy (ATT). Hopefully, by conducting this research, we are able to provide valid data that demonstrate the advantages/disadvantages usage of Anti-Tuberculosis Therapy in patients with idiopathic uveitis IGRA positive that correlate with type I IFN. This research is a part of our efforts in discovering bio-marker candidates of idiopathic uveitis IGRA positive clinical patients who will benefit from the ATT administration.

Conditions

Tuberculosis; Uveitis (Manifestation); Anti-Tuberculous Drug Reaction; Tuberculous Uveitis

Keywords

Idiopathic uveitis; IGRA positive; Type 1 interferon; Transcriptomic analysis; Anti-Tuberculosis Therapy

Outcome Measures

Primary Outcomes (2)

• Proportion of clinical improvement

  Clinical improvement of uveitis patients with IGRA positive after receiving complete Anti Tuberculosis Therapy is measured by using The Standardization of Uveitis Nomenclature (SUN) inflammation degree. Clinical improvement definition is decreasing of inflammation degree up to two degrees or becoming 0 degree. Meanwhile, clinical failure is defined by increasing of inflammation degree or decreasing of inflammation degree up to one degree/ not becoming 0 degree or unchanged degree of first to fourth degree.

  0, 14 days, 8 weeks, 3 months, 6 months, and 12 months

• The changes of type 1 interferon scoring in selected gene expression

  The score changes of type 1 interferon of uveitis patients with IGRA positive are determined by gene expression value of 10 varieties of type 1 interferon using Quantitative Reverse Transcriptase PCR (RT-qPCR) testing.

  0, 14 days, 6 months.

Study Arms (1)

Observational cohort group

Subjects: idiopathic uveitis with IGRA positive. Examinations: * Clinical improvement examinations at day 0, second week, week 8, month 3, month 6 and month 12. * Blood sampling at day 0, second week, month 6 for analysing type 1 IFN gene expression scoring using RT-qPCR methods.

Drug: Fixed drug combination (FDC) of ATT and Oral steroid

Interventions

Fixed drug combination (FDC) of ATT and Oral steroid DRUG

In the first two week, patients receive FDC of ATT only. Oral steroid start to be given in week three. The ATT regiment is continued for up to 6 months or more, in accordance with WHO guidelines. In the first two months the antibiotic combination given consisted of isoniazid (INH), rifampicin, pyrazinamide, and ethambutol. The next four months or continuation phases, the ATT given is rifampicin and isoniazid. The following dosage and administration of oral steroids will be given to patients, according to guidelines from the American Journal of Ophthalmologists (Douglas A. Jabs et al, 2000): Initial dose: 1mg/kg/day, with maximum adult oral dose 60-80 mg/kg and maintenance dose less than or equal to 10 mg/day. The tapering schedule: Over 40 mg/day, decrease by 10 mg/day every 1-2 weeks, 40-20 mg/day, decrease by 5 mg/day every 1-2 weeks, 20-10 mg/day, decrease by 2.5 mg/day every 1-2 weeks, 10-0 mg/day, decrease by 1 to 2.5 mg/day every 1-4 weeks.

Observational cohort group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Idiopathic uveitis patients with IGRA positive registered from September 2019 at Cipto Mangunkusumo Hospital

You may qualify if:

• Subjects who will be recruited to this study are patients who met the criteria described below:
• Registered patients from September 2019 at Cipto Mangunkusumo Hospital
• Idiopathic uveitis patients (proven having negative result by available etiological uveitis work-ups) with IGRA positive. IGRA positive value is defined by score above 0.35 u/ml obtained from Quantiferon Tuberculosis (QFT)-Gold Assay (QIAGEN).
• Minimum age: 18 years old
• Proven not having active Tuberculosis
• Not previously received Anti Tuberculosis Therapy.
• Not consuming antibiotic one to two weeks prior to the time of study
• Not living together with Tuberculosis active patient
• Not having plan to become pregnant during the time of study
• Not part of reactive Tuberculosis risk group based on Latent Tuberculosis Incident WHO guidelines 2018
• Active inflammation in the past 180 days characterized by the following sign based on SUN Criteria(in at least one eye)
• ≥ 2+ anterior chamber cells
• ≥ 2+ vitreous haze
• active retinal or choroidal lesions
• Active inflammation during patient registration, characterized by the following sign based on SUN Criteria (in at least one eye)

You may not qualify if:

• Not willing to sign informed consent
• Pregnant patient
• Not coming to scheduled visit date
• Uveitis caused by infectious origin
• Media opacity caused by cataract and/ or corneal scar resulting in difficulty of posterior segment examination in both eyes
• Chronic hypotony (IOP \< 5 mm Hg for \> 3 months) in both eyes
• History of prior intraocular surgery in \< 30 days, or arranged surgery within the next 6 months
• Best spectacle-corrected visual acuity (BSCVA) of hand motions or worse in better eye
• Any history of cancer excluding non-melanoma skin cancer
• Abnormal Complete blood count (≤ 2,500 white blood cells and/or ≤ 75,000 platelets and/or ≤9 hemoglobin) within 4 weeks prior to enrollment\^
• Abnormal alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≥ 2 times the upper limit of normal for the lab and/or creatinine ≥ 1.5 within 4 weeks prior to enrollment\^
• Patient with active infection of tuberculosis, HIV infection, syphilis, or hepatitis B or C
• Note (\^): Testing is conducted within 1-2 weeks prior to enrollment;
• As many 10 subjects of the health volunteers are recruited for this study after giving consent. The health volunteers that will be recruited are the subject who met following criteria:
• age: 18-50 years old (Man/Woman)

Sponsors & Collaborators

• Fakultas Kedokteran Universitas Indonesia: lead

Study Sites (1)

RSUPN dr. Cipto Mangunkusumo (Cipto Mangunkusumo Hospital)

Jakarta Pusat, Jakarta Special Capital Region, 10430, Indonesia

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood from the patients are collected in PAXgene blood RNA tubes (QIAGEN). The RNA from the whole blood is extracted and proceed for further examinations (type 1 interferon expression and transcriptomic analysis).

MeSH Terms

Conditions

Tuberculosis; Uveitis

Interventions

Steroids

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Uveal Diseases; Eye Diseases

Intervention Hierarchy (Ancestors)

Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Rina La Distia Nora

  Division of Ophthalmology Departement, Faculty of Medicine Universitas Indonesia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rina La Distia Nora

CONTACT

+62811-198-910; rina.ladistia@ui.ac.id

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 1 Year
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Lecturer

Study Record Dates

• First Submitted: September 11, 2019
• First Posted: September 12, 2019
• Study Start: October 30, 2019
• Primary Completion: July 1, 2024
• Study Completion: July 1, 2024
• Last Updated: February 28, 2024

Record last verified: 2024-02

Locations

ID (1)