Phase II study on the safety and efficacy of cysteamine in association with standard tuberculosis therapy for the treatment of patients with pulmonary tuberculosis: a new therapy for tuberculosis directed at the host

Phase 1

• Conditions: Pulmonary Mycobacterium tuberculosis infection; MedDRA version: 20.0Level: PTClassification code 10037440Term: Pulmonary tuberculosisSystem Organ Class: 10021881 - Infections and infestations; Therapeutic area: Diseases [C] - Bacterial Infections and Mycoses [C01]

• Registration Number: EUCTR2019-002514-40-IT
• Lead Sponsor: ISTITUTO NAZIONALE PER LE MALATTIE INFETTIVE LAZZARO SPALLANZANI

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-05-24
• Last Update Posted: 30 August 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

• Age between 18 and 65;
• Clinical signs and symptoms of pulmonary tuberculosis (new diagnosis)
• Abnormal chest x-ray compatible with pulmonary tuberculosis
• At least one positive sputum for acid-resistant bacteria (BAAR) (bacterisoscopic examen) [and molecular confirmation for M. tuberculosis by Xpert Mycobacterium tuberculosis (MTB) / rifampicin resistance (RIF) with a cycle threshold (Ct) <28.
• Sensitivity to antituberculosis drugs by phenotypic pharmacosensitivity test on MGIT liquid medium
• Weight =>50 kg
• Karnofsky score of at least 60
• Levels of leukocyte cystine (<2 nmol hemicystine / mg protein)
• Ability to provide informed consent
• Ability to adhere to control visits
• Consent to be hospitalized for 4 weeks
• Consent to perform a treatment under direct observation
• Consent to comply with the following contraception requirements for people of childbearing age starting 2 weeks before enrollment at 18 weeks after the drug was administered:
- Vasectomy with documented azoospermia for male subjects
- Use of the condom for male subjects or one of the following contraceptive methods by the partner: Combined hormonal contraceptives associated with ovulation inhibitors (oral, intravaginal, transdermal), Progestinal hormonal contraceptives associated with an ovulation inhibitor (oral, injectable, implantable), Intrauterine devices, Intrauterine devices with hormonal release system, Bilateral tubal binding, Partner's vasectomy,
- Sexual abstinence;

The infertility condition in female subjects will be defined:
- In the pre-menopausal phase with: documented tubal closure; documented hysteroscopic tubal occlusion procedure, hysterectomy, documented ovariectomy
- Post-menopausal phase: with 12 months of spontaneous amenorrhea and confirmation by hormonal dosage

• Consent to carry out a pregnancy test before the administration of the experimental drug for female subjects of childbearing age
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 30
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

• Age> 65 years and <18 years
• Use of antiretroviral drugs
• Hemoglobin concentration under 10 g / dl
• Elevation of creatinine kinase at baseline more than three times the upper limit of normal
• Abnormal baseline laboratory values ¿¿(baseline concentration of alanine aminotransferase (ALT) more than three times the upper limit of normal, serum creatinine concentration more than twice the upper limit of normal, total bilirubin serum level greater than twice the upper limit of normal, platelet count <100,000 / mm3, white blood cells (WBC) <2500 (mcL)
• Pregnancy or breast-feeding
• Silico-Tuberculosis
• Previous anti-tuberculosis treatment or use for more than 5 days of anti-tuberculosis drugs in the 3 months prior to enrollment
• Concomitant diseases or conditions for which anti-tuberculosis drugs are contraindicated. These include severe liver failure, acute arthritis, peripheral neuropathy
• Presence of any physical or psychological condition which, according to the person responsible of the study, makes participation in the study inadvisable
• Infection with an isolate known to be resistant to a first drug for tuberculosis, for example rifampicin
• Scheduled or current use of cyclosporine, tacrolimus, erythromycin or colchicine
• TB with extra-pulmonary localization
• Therapy with immunosuppressive drugs and / or NSAIDs and / or cortisone drugs
• TB resistant to first and second line drugs
• Inability to understand and sign informed consent
• Positivity for HIV, HCV, HBV (HBsAg positivity)
• Hepatic impairment (Child A-C), Renal failure (creatinine clearance <50 ml / min), heart failure (NYHA III-IV), decompensated diabetes mellitus, neoplasms, ongoing neurological / psychiatric pathology (eg depression, psychotic crisis, suicide attempt), inflammatory bowel diseases or gastric ulcer / duodenal treatment, autoimmune diseases
• Abuse of drugs / alcohol
• Hypersensitivity to cysteamine or penicillin
• Current use of cysteamine
• Participation in other Clinical Trials

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified