A Phase 1 interventional study of Autologous T-regulatory lymphocytes and Interleukin-2 in ALS (Amyotrophic Lateral Sclerosis), sponsored by The Methodist Hospital Research Institute. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-06-17.
Sponsored by The Methodist Hospital Research Institute · Phase 1, Interventional, and Treatment
Open-label pilot study to determine the safety and tolerability of autologous CD4+ CD25+ regulatory T cells infusions with concomitant subcutaneous IL-2 injections taken 3 times per week in 3 participants with ALS.
This is Pilot Study will consist of 3 people diagnosed with amyotrophic lateral sclerosis (ALS), who will undergo 4 infusions of autologous expanded Tregs and concomitant subcutaneous injections of Interleukin-2 [IL-2] (2 x 105 IU/m2) 3 times weekly, for 52 weeks or unless the interim analysis confirms or negates the investigational product (IP = Tregs) use.
During the enrollment period up to three research participants will be recruited from patients in our ALS Clinic for screening, baseline measures and leukapheresis. The Treg cell manufacturing will be performed in a current Good Manufacturing Practice (cGMP) laboratory. The first subject will receive infusions of their expanded Tregs (1x106 /kg) with concomitant subcutaneous IL-2 injections (2 x 105 IU/m2) 25 days (+/- 2 days) post leukapheresis. The 2nd subject will begin after the first subject has completed the first 4 weeks and has experienced no untoward effects during this period. Once subjects #1 and #2 have completed the first 4 weeks and no toxic events have occurred they will therefore be considered safely past the first milestone and subject #3 will begin infusions.
Research Participants #1, 2 and 3 will repeat the leukapheresis (under a separate protocol) and undergo Treg infusions at the modified schedule of every 4 weeks, with concomitant subcutaneous injections of IL-2 (2 x 105 IU/m2) 3 times weekly. The subjects will be called on Day 7, and 21. Office visits will be completed on the day after infusions and every two weeks while the subjects are undergoing Treg infusions for clinical evaluation, scoring, and blood draws. The subjects will then be seen during office visits once per month for one year total from their initial baseline visit for clinical evaluation, scoring, and blood draws
Monthly interim analyses will monitor the subjects using validated ALS scales such as the ALS Functional Rating Scale-Revised (ALSFRS-R) and Appel ALS Grading Scale (AALS), which incorporates muscle strength and dysfunction, activities of daily living and pulmonary function. The analyses will also include interim medical history and physical exam, an electrocardiogram (ECG) when indicated, pulmonary function tests (PFTs) such as Forced vital capacity (FVC) and Maximum Inspiratory Pressure (MIP or MIPS), safety labs (such as a complete blood count (CBC), chemistry, liver function, thyroid tests-T4 and TSH) as well as more technical research labs such as T Regulatory Cell and related markers (Th1 and Th17 counts, FoxP3 RNA expression), and Treg Suppression Assays. A prothrombin time (PT) and partial thromboplastin time (PTT) will be performed only if the subject has an abnormal coagulation result at baseline or if the subject is on anti-coagulation therapy.
Adverse Events (AEs) and Serious Adverse Events (SAEs) will be monitoring from the time of consent until end of study or AE/SAE resolution.
981 studies on the registry are indexed under Amyotrophic Lateral Sclerosis; 283 are open to participants now.
This study's enrollment of 3 is below the median of 36 across 667 interventional studies indexed under Amyotrophic Lateral Sclerosis.
Browse Amyotrophic Lateral Sclerosis studies →The Methodist Hospital Research Institute is the lead sponsor of 157 studies on the registry; 60 are open to participants now.
Of its 25 completed or terminated interventional studies of FDA-regulated products, 15 (60%) have results posted.
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Exclusion Criteria:
All subjects are enrolled in the one arm consisting of infusions of autologous T-regulatory lymphocytes at a dose of 1x10 to the sixth/kg and subcutaneous injections of Interleukin-2 at a dose of 2x10 to the fifth IU/m2 three times a week.
Biological: Autologous T-regulatory lymphocytes · Biological: Interleukin-2
intravenous administration of Autologous T-regulatory lymphocytes at a dose of 1x10 to the sixth /kg.
Subcutaneous Interleukin-2 at a dose of 2x10 to the fifth IU/m2, three times a week.
Also known as: IL-2
Number of Participants With Treatment-related Adverse Events as Assessed by Common Terminology Criteria for Adverse Events (CTCAE v4.0) & Medical Dictionary for Regulatory Activities (MedDRA).
Adverse events and serious adverse events related to Treg infusions were monitored throughout the study.
Time frame: Adverse events related to Treg infusions at Baseline to up to two years or study participation, whichever is occurs first.
Appel ALS (AALS) Scale/Grading
The AALS is a published, validated instrument based on objective testing in five categories (bulbar, respiratory function, arm and leg function, and muscle strength) with scores ranging from 30 (normal) to 164 (maximally impaired).
Time frame: Baseline and at week 15
ALSFRS-R (Amyotrophic Lateral Sclerosis 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 a person's assessment of their capability and independence in 12 functional activities based on 10 questions related to motor, bulbar and respiratory function. Participants are asked to rate his/her impression of function regarding writing, self care, climbing stairs, and breathing. Each task is rated on a five-point scale from 0 = can't do to 4 = normal ability resulting in an overall score of 0 (worst) to 48 (best).
Time frame: Baseline to week 15
T-Regulatory Cells
Treg percentage (CD4+CD25+FOXP3+ cells) within the total CD4+ population will be assessed by multicolor flow cytometry. Cluster of differentiation 4 (CD4 ) cells are also known as T cells, the white blood cells, which fight infection and play an important role in the immune system.
Time frame: Mean and standard deviation represent the average of baseline and 3-month assessments.
Treg Suppression
Treg suppressive function of T-effector (Teff) cells will be assessed by \[3H\]-thymidine incorporation. 3H-thymidine is a radioactive nucleoside that is incorporated into a commonly used assay to measure lymphocyte proliferation. Correlation between changes in the rate of disease progression and the Treg percentage and function will be determined by Spearman's correlation analysis.
Time frame: Baseline to 3 months post treatment for a total of two years from baseline
T Helper Cells Type 1 (Th1) Lymphocytes
The percentage of Tregs, Th1 lymphocytes, assessed by multicolor flow cytometry.
Time frame: Baseline to 3 months post-treatment for a total of two years from baseline
Pulmonary FVC - Exploratory Measure - Percent of Predicted FVC
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. The intent is to report the percent of predicted FVC value.
Time frame: Mean and standard deviation of the values from baseline and 3 months.
Pulmonary MIP - Exploratory Measure
MIP (Maximum Inspiratory Pressure) measures the strength of muscles used during inspiration and assessed due to decreased pulmonary function resulting in a primary source of ALS morbidity and mortality. MIP is the lowest pressure developed during a forceful inspiration against an occluded airway, measured with a device during maximal inspiration from 0 (worst) to 100 (best) and recorded as a number with the units, cm H2O (centimeters of water). Declining MIP indicates worsening of pulmonary function and maintenance of MIP over time indicates the goal of sufficient/stable respiratory strength.
Time frame: At Baseline and at 3 months intervals, up to two years from baseline (or as long as participant is involved in the study).
Need for Tracheostomy- Exploratory Measure
Number of patients requiring a tracheostomy. Patients undergoing an elective, prophylactic or required tracheostomy is performed when a patient may not maintain adequate ventilation with non-invasive ventilation \[such as bilevel positive airway pressure (BIPAP) or average volume-assured pressure support (AVAPS)\], or could not produce adequate cough with a cough assist device to manage their secretions.
Time frame: Baseline to 3 months post-treatment
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; values less than 75% are indicative of the need for intervention and/or monitoring and optimal FVC values are greater than 76%.
Time frame: Baseline to 3 months post-treatment for a total of two years from baseline
Enrollment began 2/2016 and ended 9/1/2016, with the clinic identifying patients with a sporadic or familial amyotrophic lateral sclerosis (ALS) diagnosis.
| Milestone | Treatment Arm |
|---|---|
| Started | 3 |
| Completed | 2 |
| Not completed | 1 |
| Withdrew: Withdrawal by subject | 1 |
Adverse events and serious adverse events related to Treg infusions were monitored throughout the study.
| Participants | Treatment Arm |
|---|---|
| Number of Participants With Treatment-related Adverse Events as Assessed by Common Terminology Criteria for Adverse Events (CTCAE v4.0) & Medical Dictionary for Regulatory Activities (MedDRA). | 0 |
The AALS is a published, validated instrument based on objective testing in five categories (bulbar, respiratory function, arm and leg function, and muscle strength) with scores ranging from 30 (normal) to 164 (maximally impaired).
| units on a scale | Treatment Arm |
|---|---|
| Baseline Appel ALS Grading | 50 ± 7.87 |
| Week 15 Appel ALS Grading | 68 ± 12.36 |
| Change from Baseline to Week 15 | 10.4 ± 6.84 |
The ALSFRS-R (ALS Functional Rating Scale-Revised) is an orally administered validated instrument using an ordinal rating scale used to determine the a person's assessment of their capability and independence in 12 functional activities based on 10 questions related to motor, bulbar and respiratory function. Participants are asked to rate his/her impression of function regarding writing, self care, climbing stairs, and breathing. Each task is rated on a five-point scale from 0 = can't do to 4 = normal ability resulting in an overall score of 0 (worst) to 48 (best).
| score on a scale | Treatment Arm |
|---|---|
| Baseline ALS FRS-r | 40.3 ± 3.3 |
| Week 15 ALS FRS-r | 38 ± 4.2 |
| Change between Baselines & Week 15 ALS FRS-r | 2.33 ± 1.7 |
Treg percentage (CD4+CD25+FOXP3+ cells) within the total CD4+ population will be assessed by multicolor flow cytometry. Cluster of differentiation 4 (CD4 ) cells are also known as T cells, the white blood cells, which fight infection and play an important role in the immune system.
| percentage of Tregs | Treatment Arm |
|---|---|
| T-Regulatory Cells | 2.9 ± 0.19 |
Treg suppressive function of T-effector (Teff) cells will be assessed by \[3H\]-thymidine incorporation. 3H-thymidine is a radioactive nucleoside that is incorporated into a commonly used assay to measure lymphocyte proliferation. Correlation between changes in the rate of disease progression and the Treg percentage and function will be determined by Spearman's correlation analysis.
| percentage of cells | Treatment Arm |
|---|---|
| Baseline %Treg suppressive function of Teffectors | 37.1 ± 17.2 |
| Month 3 %Treg suppressive function of Teffectors | 49 ± 16.5 |
The percentage of Tregs, Th1 lymphocytes, assessed by multicolor flow cytometry.
| percentage of cells | Treatment Arm |
|---|---|
| Baseline % of Th1 lymphocytes | 85.1 ± 3.4 |
| Month 3 % of Th1 lymphocytes | 81.3 ± 0.8 |
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. The intent is to report the percent of predicted FVC value.
| percentage of predicted FVC | Treatment Arm |
|---|---|
| Baseline FVC | 75 ± 14.8 |
| Month 3 FVC | 75.7 ± 25.1 |
| Change from Baseline to Month 3 FVC | 9.33 ± 4.49 |
MIP (Maximum Inspiratory Pressure) measures the strength of muscles used during inspiration and assessed due to decreased pulmonary function resulting in a primary source of ALS morbidity and mortality. MIP is the lowest pressure developed during a forceful inspiration against an occluded airway, measured with a device during maximal inspiration from 0 (worst) to 100 (best) and recorded as a number with the units, cm H2O (centimeters of water). Declining MIP indicates worsening of pulmonary function and maintenance of MIP over time indicates the goal of sufficient/stable respiratory strength.
| cm H2O | Treatment Arm |
|---|---|
| Baseline MIP | 90 ± 29.4 |
| Post-3months from Baseline MIP | 85 ± 36.3 |
| Change from Baseline to 3Months | 5 ± 7.07 |
Number of patients requiring a tracheostomy. Patients undergoing an elective, prophylactic or required tracheostomy is performed when a patient may not maintain adequate ventilation with non-invasive ventilation \[such as bilevel positive airway pressure (BIPAP) or average volume-assured pressure support (AVAPS)\], or could not produce adequate cough with a cough assist device to manage their secretions.
| participants | Treatment Arm |
|---|---|
| Baseline Tracheostomy | 0 |
| Tracheostomy placed after Treg infusions | 0 |
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; values less than 75% are indicative of the need for intervention and/or monitoring and optimal FVC values are greater than 76%.
| percentage of predicted FVC value | Treatment Arm |
|---|---|
| Pulmonary FVC - Exploratory Measure | 75.35 ± 7.3 |
Collected over Adverse events (AEs) and serious adverse events (SAEs) were systematically monitored and assessed for each participant from the time of informed consent through 1 month following trial exit, an average of 2 years from baseline.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Treatment Arm | 3/3 (100%) | 0/3 (0%) | 1/3 (33.3%) |
| Event | Treatment Arm |
|---|---|
| Facial ecchymosis post fallInjury, poisoning and procedural complications | 1/3 |
| Mandible FractureMusculoskeletal and connective tissue disorders | 1/3 |
| PharyngitisInfections and infestations | 1/3 |
| Nocturnal Muscle CrampingMusculoskeletal and connective tissue disorders | 1/3 |
| Urinary Tract InfectionInfections and infestations | 1/3 |
| Dysphagia worsened during studyGastrointestinal disorders | 1/3 |
| urinary retention following PEG placementRenal and urinary disorders | 1/3 |
| aspiration pneumonia related to worsening bulbar ALSRespiratory, thoracic and mediastinal disorders | 1/3 |
| gastroenteritisGastrointestinal disorders | 1/3 |
| Suspected upper respiratory infectionInfections and infestations | 1/3 |
Sporadid or familial Amyotrophic Lateral Sclerosis
| Age, Categorical(Participants) | Treatment Arm |
|---|---|
| <=18 years | 0 |
| Between 18 and 65 years | 3 |
| >=65 years | 0 |
| Age, Continuous(Years) | Treatment Arm |
|---|---|
| Mean | 50 ± 5.3 |
| Sex: Female, Male(Participants) | Treatment Arm |
|---|---|
| Female | 1 |
| Male | 2 |
| Race (NIH/OMB)(Participants) | Treatment Arm |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 0 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 0 |
| White | 3 |
| More than one race | 0 |
| Unknown or Not Reported | 0 |
| Region of Enrollment(participants) | Treatment Arm |
|---|---|
| United States | 3 |
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Amyotrophic Lateral Sclerosis→
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