2024-516088-10-00招募中2 期
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.
National Institute For Infectious Diseases Lazzaro Spallanzani1 个研究点 分布在 1 个国家目标入组 30 人开始时间: 2024年10月21日最近更新:
适应症
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Acceptability of treatment
研究概览
简要总结
Investigate in an off-label phase II study in adult patients with bacilliferous pulmonary TB, the safety and tolerability of using cysteamine as adjunctive therapy to standard TB treatment
入排标准
- 年龄范围
- 18 years 至 64 years（18-64 Years）
- 接受健康志愿者
- 是
入选标准
- •Age between 18 and 65 years
- •Clinical signs and symptoms of pulmonary tuberculosis (new diagnosis)
- •Abnormal chest radiograph compatible with pulmonary tuberculosis
- •At least one positive sputum for alcohol-acid-resistant bacteria (BAAR) (bacterisoscopic examination) and molecular confirmation for M. tuberculosis by DNA detection of M. tuberculosis complex with a cycle threshold (Ct) <40, associated with possible genotypic resistance finding to rifampin and isoniazid
- •Sensitivity to first-line antitubercular drugs by phenotypic pharmacosensitivity test on MGIT liquid medium
- •Infertility status in females. A woman is considered to be potentially fertile, or fertile, after menarche and until she enters postmenopause, unless she is permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy. Postmenopausal status is defined as the absence of menses for 12 months without an alternative medical cause. An elevated follicle-stimulating hormone (FSH) level in the postmenopausal range can be used to confirm postmenopausal status in women who are not using hormonal contraceptives or hormone replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is not sufficient. Therefore, for the purposes of this protocol, infertility status in females will be defined as: Premenopausal with: documented bilateral salpingectomy, hysterectomy, documented bilateral oophorectomy. In the post-menopausal phase: with 12 months of spontaneous amenorrhea and confirmation
- •Body Weight ≥50 kg
- •Karnofsky score ≥60 %
- •Ability to provide informed consent
- •Ability to adhere to follow-up visits
- •Consent to be hospitalized for 4 weeks
- •Consent to treatment under direct observation
- •Consent to adhere to contraception requirements for subjects of childbearing age from 2 weeks prior to enrollment to 18 weeks after experimental drug administration
- •Consent to perform a pregnancy test prior to administration of the experimental drug for female subjects of childbearing age
排除标准
- •Age > 65 years and <18 years
- •Concomitant diseases or conditions for which anti-tubercular drugs are contraindicated. These include severe liver failure, acute arthritis, peripheral neuropathy..
- •Presence of any physical or psychological condition that, in the opinion of the principal investigator, makes participation in the study contraindicated
- •Planned or current use of cyclosporine, tacrolimus, erythromycin or colchicine
- •TB with extra-pulmonary localization
- •Therapy with immunosuppressant drugs and/or NSAIDs and/or corticosteroids in the 4 weeks prior at enrollment
- •TB resistant to first- and second-line drugs
- •Inability to understand and sign informed consent
- •Seropositivity for HIV, HCV, HBV (HBsAg positivity)
- •Liver failure (Child B-C), renal failure (creatinine clearance < 50 ml/min), heart failure (NYHA III-IV), decompensated diabetes mellitus, neoplasms (those who have had cycles of chemotherapy including biologic drugs and/or radiation therapy in the past 5 years), ongoing neurological/psychiatric pathology (e.g. depression, psychotic break, suicide attempt), chronic inflammatory bowel disease or gastric/duodenal ulcer under treatment, autoimmune disease
- •Drug/alcohol abuse
- •Body weight < 50 kg
- •Hypersensitivity to cysteamine or penicillin
- •Current use of cysteamine
- •Participation in other Clinical Trials.
- •Hemoglobin concentration less than 10 g/dl
- •use of antiretroviral drugs
- •Increasing of creatinine kinase at baseline more than three times the upper limit of normal
- •Abnormal laboratory values at baseline (baseline alanine aminotransferase (ALT) concentration more than three times the upper limit of normal, serum creatinine concentration more than twice the upper limit of normal, serum total bilirubin level more than twice the upper limit of normal, platelet count <100,000/mm3, white blood cell (WBC) <2500 (mcL)
- •Pregnancy or breastfeeding
- •Silico-tuberculosis
- •Previous anti-tubercular treatment or use for more than 5 days of anti-tubercular drugs in the 3 months prior to enrollment
结局指标
主要结局
Acceptability of treatment
Acceptability of treatment
Adherence: doses taken/expected doses of cysteamine.
Adherence: doses taken/expected doses of cysteamine.
Tolerability of treatment.
Tolerability of treatment.
Pharmacokinetics of all administered drugs performed on plasma (dedicated test tube with EDTA as anticoagulant).
Pharmacokinetics of all administered drugs performed on plasma (dedicated test tube with EDTA as anticoagulant).
Evaluation of serious adverse events (SAEs) and unexpected events.
Evaluation of serious adverse events (SAEs) and unexpected events.
Correlation of any AEs and SAEs with pharmacokinetic profiles.
Correlation of any AEs and SAEs with pharmacokinetic profiles.
次要结局
- Evaluate the effect of cysteamine on Mtb by molecular assay for bacterial load assessment (MBLA) at different time points (day 0, 7±1 and 28±3).
- (Additional endpoint). Evaluation of biomarkers useful for therapy monitoring in different biological samples (blood, plasma, serum, cells, urine, sputum) at different time points [day 0, 7±1, 14±1, 28±3,60±3, end of therapy (month 6±3)] ((for example, cytokines/chemokines, cell counts, inflammatory factors, biochemical factors will be evaluated by multiparametric immunohistochemical methods and/or immunometric/enzymatic assays).
- (Additional Endpoints). Immunological characterization of cysteamine activity. In particular, at different time points [day 0, 7±1, 14±1, 28±3, 60±3, end of therapy (month 6±3)], the following will be evaluated in peripheral blood mononuclear cells (PBMC) stimulated with Mtb-specific stimuli: cellular activation markers, cytokine production and memory profile (e.g. CD3, CD4, CD8, CD19, CD45RA, CD27, CCR7, CD38, CD25, HLA-DR, IFN-γg, TNF-αa,IL-2)by flow cytometry.Transcriptome will be evaluated
研究者
Fabrizio Palmieri
Scientific
National Institute For Infectious Diseases Lazzaro Spallanzani
研究点 (1)
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