Tofacitinib tablets: All patients should be closely monitored for signs and symptoms of infection during and after treatment with tofacitinib tablets. If a patient develops a severe infection, opportunistic infection, or sepsis, medication should be discontinued. During treatment, patients with lymphocyte counts \< 500 cells/mm\^3 or ANC \< 500 cells/mm\^3 confirmed by repeated testing should be stopped. When 500≤ANC≤1000 cells/mm\^3, administration should be interrupted, and if ANC returns to more than 1000 cells/mm\^3, administration should be resumed. When hemoglobin \< 8 g/dL or decreases by more than 2 g/dL, administration should be interrupted until hemoglobin values return to normal.
Study summary
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease, of which motor-neuron's degeneration may be associated with neuroinflammation. Tofacitinib is a Janus kinase (JAK) inhibitor that affects cellular hematopoiesis and cellular immune function. At the same time, tofacitinib is suitable for rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. This study is a single center, single arm, proof of concept, clinical trial study, and it is planned to use tofacitinib to carry out a clinical trial to observe the treatment effect of ALS patients.
Eligibility
Sex
ALL
Min age
18 Years
Max age
75 Years
Healthy volunteers
No
Inclusion Criteria:
* 18 years old≤ age≤ 75 years old, males or females;
* Forced vital capacity ≥ 60% of predicted vital capacity during the screening period;
* The diagnosis conforms to the diagnostic criteria for amyotrophic lateral sclerosis on the Gold Coast;
* Based on the analysis of whether the subject significantly deviates from the baseline healthy elderly population, whole exome sequencing (WES) revealed that the embryonic lineage etiology was interpreted as CD8+ T lymphocyte group and Th1 highly activated, and patients with pathways related to neural repair and energy metabolism pathways that were not significantly inhibited;(1.Obtain genomic data of patient embryonic samples (blood or oral swab) through whole exome sequencing (WES) technology;2.Utilizing the Damage Assessment of Genome shotgun (DAGG) system developed by the Turing Darwin Laboratory team, rare coding mutations in patient genomic data are converted into an activity profile of signaling pathways (APSP). If the patient's embryonic genomic interpretation of APSP compared to the baseline healthy population's embryonic APSP shows high activation of CD8+ T lymphocyte group and Th1 activity, and non-significant inhibition of Treg, neural repair, and energy metabolism pathways, the patient may be included in the clinical trial;3.This step is analyzed by the Turing Darwin Laboratory team, and based on the entry criteria of the clinical trial (high activation of CD8+ T lymphocyte group and Th1 activity, and non-significant inhibition of Treg, neural repair, and energy metabolism pathways), a modeling setting for the APSP score threshold for ALS will be established. Patients above the threshold can be included in the trial.
* Subjects or their legal representatives clearly understand and voluntarily participate in the study and sign the informed consent form;
* Subjects (including male subjects) are willing to have no birth plan and voluntarily take effective contraceptive measures during the entire study period and within 3 months after the end of the study, and have no plan to donate sperm or eggs.
Exclusion Criteria:
* Patients who cannot cooperate with the clinical trial project cycle as determined by professional medical staff;
* Individual whose use of tofacitinib is forbidden;
* Absolute lymphocyte counts \< 500 cells /mm\^3, absolute neutrophil counts (ANC) \< 1000 cells /mm\^3 or hemoglobin level \< 9 g/dL;
* Serious infection;
* Positive HIV test or history of positive test;
* Positive hepatitis C virus antibody or positive test history;
* Hepatitis B active infection (hepatitis B surface antigen positive and/or serum HBV DNA positive or serum HBV DNA \> 2 × 10\^8 IU/mL;
* Positive syphilis test result or positive test history;
* Lumbar spine diseases or malformation;
* Have other conditions known to be associated with motor neuron dysfunction that may confuse or obscure an ALS diagnosis;
* Other psychiatric disorders diagnosed according to DSM-V diagnostic criteria, or significant suicide intent;
* With severe hepatic insufficiency, renal insufficiency or severe cardiac insufficiency (severe hepatic insufficiency refers to ALT value≥2.0 times the upper limit of normal value or AST value≥2.0 times the upper limit of normal value; severe renal insufficiency refers to CRE≥1.5 times the upper limit of normal value or eGFR\<40mL/min/1.73m\^2; severe cardiac insufficiency refers to NYHA class 3-4);
* Permanently dependent on ventilator-assisted ventilation;
* Individual who have difficulty communicating verbally to the extent that they are unable to communicate, understand or follow instructions normally, and are unable to cooperate with treatment and evaluation;
* History of alcohol and drug abuse;
* Patients who are pregnant, breast-feeding, or who are likely to become pregnant and plan to become pregnant;
* Patients participating in other clinical trials or using other biological agents, drugs, or devices under investigation;
* Unable to be cooperative and complete the follow-up due to other reasons.
Primary outcome measure(s)
Changes of ALSFRS-R scale scores in ALS patients — day 180±14 Amyotrophiclateral sclerosis functional rating scale revised(ALSFRS-R) is the most common evaluation indicator in ALS related research, with scores ranging from 0 to 48. The higher the score, the better the functional retention and the milder the symptoms.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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