ALS (Amyotrophic Lateral Sclerosis) Clinical Trial
Official title:
Expansion and Infusion of T-Regulatory Cells in Amyotrophic Lateral Sclerosis
Verified date | March 2018 |
Source | The Methodist Hospital System |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
This is an open-label pilot study to determine the safety and tolerability of infusions of autologous CD4+ CD25+ regulatory T cells with concomitant subcutaneous IL-2 injections in 4 subjects with ALS.
Status | Active, not recruiting |
Enrollment | 4 |
Est. completion date | March 2018 |
Est. primary completion date | February 2018 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility |
Inclusion Criteria: 1. Age 18 years or older. 2. Sporadic or familial ALS diagnosed as possible, laboratory-supported probable, probable, or definite as defined by revised El Escorial criteria (Appendix 1). 3. Subjects must not have taken riluzole for at least 30 days, or be on a stable dose of riluzole for at least 30 days (riluzole-naïve subjects are permitted in the study). 4. Capable of providing informed consent and following trial procedures. 5. Geographically accessible to the site. 6. Women must not be able to become pregnant (e.g. post-menopausal, surgically sterile, or using adequate birth control methods) for the duration of the study and three months after study completion. Adequate contraception includes: abstinence, hormonal contraception (oral contraception, implanted contraception, injected contraception or other hormonal (patch or contraceptive ring, for example) contraception), intrauterine device (IUD) in place for = 3 months, barrier method in conjunction with spermicide, or another adequate method. 7. Subjects must agree not to take live attenuated vaccines (including seasonal flu vaccine) 30 days before blood collection. 8. Available autologous Tregs product with greater than or equal to 50% expression of CD4, CD25 and FoxP3 determined by flow-cytometry. 9. Subjects must have been previously evaluated and followed clinically by a neuromuscular specialist at Houston Methodist Neurological Institute 10. Normal Alanine aminotransferase level (ALT) 11. Normal Serum creatinine level Exclusion Criteria: 1. Prior use of cells therapies 2. Concurrent use of other experimental ALS therapies 3. Pregnant or breastfeeding or planning to become pregnant or planning a partner's pregnancy. 4. Other unstable medical or psychiatric illness 5. Known immune deficiency or history of lymphoma or leukemia 6. History of lymphopenia. 7. History of acquired or inherited immune deficiency syndrome, including leukopenia. 8. History of severe untreated chronic obstructive sleep apnea. 9. FVC less than 50% predicted at screening. 10. Exposure to any other agent currently under investigation for the treatment of subjects with ALS (off-label use or investigational) within 30 days of the Baseline Visit. 11. The presence of unstable psychiatric disease, cognitive impairment, or dementia that would impair ability of the subject to provide informed consent, according to the PI's judgment, or a history of active substance abuse within the prior year. 12. Clinically significant history of cardiac, oncologic, hepatic, or renal dysfunction, or other medically significant illness. 13. The presence of any immunologic or autoimmune disease 14. Severe cardiac dysfunction defined clinically, or as a left ventricular ejection fraction less than 40% of predicted or abnormal EKG findings. |
Country | Name | City | State |
---|---|---|---|
United States | Methodist Neurological Institute | Houston | Texas |
Lead Sponsor | Collaborator |
---|---|
Stanley H. Appel, MD |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | Pulmonary FVC - Exploratory Measure | FVC (Forced Vital Capacity). Reduction of pulmonary function is the primary source of morbidity and mortality in ALS. FVC testing will be used to monitor respiratory function. FVC measures the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. | Baseline to 3 months post-treatment for a total of two years from baseline | |
Other | Pulmonary MIP - Exploratory Measure | MIP (Maximum Inspiratory Pressure. Reduction of pulmonary function is the primary source of morbidity and mortality in ALS. MIP testing will be used to monitor respiratory function. MIP measures inspiratory muscle strength. | Baseline to 3 months post-treatment for a total of two years from baseline | |
Other | Tracheostomy- Exploratory Measure | Duration of tracheostomy-free survival | Baseline to 3 months post-treatment for a total of two years from baseline | |
Primary | Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 | Clinical laboratory blood tests are standard to assure safety in clinical trials. Complete blood count, chemistry, liver function, throxine (T4) and thyroid stimulating hormone (TSH) will be assessed for normal reference ranges and abnormal (not clinically significant) results. Clinically abnormal results will be documented as adverse events as per CTCAE v4.0. | Baseline to two years | |
Secondary | AALS (Appel ALS) Scale | The AALS is a published, validated instrument that consists of five sub-scores: bulbar, respiratory, muscle strength, and lower extremity and upper extremity function. Each group is composed of individual tests. The total Appel ALS score is 30 for healthy subjects and 164 for those with maximum impairment. The rate of change in the Appel ALS Rating Scale is a significant predictor of survival for subjects with ALS. | Baseline to week 15 | |
Secondary | ALSFRS-R (ALS Functional Rating Scale-Revised) | The ALSFRS-r (ALS Functional Rating Scale-revised) is an orally administered validated instrument using an ordinal rating scale used to determine the subject's assessment of their capability and independence in 12 functional activities. The scale addresses fine motor, gross motor, bulbar and respiratory function. The ALSFRS-r is used as a clinical assessment in ALS standard of care and in most ALS clinical trials. | Baseline to week 15 | |
Secondary | T-Regulatory Cells | Treg percentage (CD4+CD25+FOXP3+ cells) within the total CD4+ population will be assessed by multicolor flow cytometry. | Baseline to 3 months post treatment for a total of two years from baseline | |
Secondary | Treg Suppression | Treg suppressive function of T-effector (Teff) cells will be assessed by [3H]-thymidine incorporation. Correlation between changes in the rate of disease progression and the Treg percentage and function will be determined by Spearman's correlation analysis. | Baseline to 3 months post treatment for a total of two years from baseline | |
Secondary | TH17 and Th1 lymphocytes | The percentage of Tregs, Th1 lymphocytes and Th17 lymphocytes will be assessed by multicolor flow cytometry. | Baseline to 3 months post-treatment for a total of two years from baseline |
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