ALS (Amyotrophic Lateral Sclerosis)Phase 1NCT03241784
Ph1 T-Regulatory Cells in Amyotrophic Lateral Sclerosis
A Phase 1 study testing Autologous T-regulatory lymphocytes and Interleukin-2 in people with ALS (Amyotrophic Lateral Sclerosis), run by The Methodist Hospital Research Institute at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- ALS (Amyotrophic Lateral Sclerosis)
- What is being tested?
- Autologous T-regulatory lymphocytes and Interleukin-2
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- 16 May 2016to 10 Apr 2018
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18 years or older.
- Sporadic or familial ALS diagnosed as possible, laboratory-supported probable, probable, or definite as defined by revised El Escorial criteria (Appendix 1).
- 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).
- Capable of providing informed consent and following trial procedures.
- Geographically accessible to the site.
- 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.
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- Subjects must agree not to take live attenuated vaccines (including seasonal flu vaccine) 30 days before blood collection.
- Available autologous Tregs product with greater than or equal to 50% expression of CD4, CD25 and FoxP3 determined by flow-cytometry.
- Subjects must have been previously evaluated and followed clinically by a neuromuscular specialist at Houston Methodist Neurological Institute
- Normal Alanine aminotransferase level (ALT)
- Normal Serum creatinine level
Who cannot join
- Prior use of cells therapies
- Concurrent use of other experimental ALS therapies
- Pregnant or breastfeeding or planning to become pregnant or planning a partner's pregnancy.
- Other unstable medical or psychiatric illness
- Known immune deficiency or history of lymphoma or leukemia
- History of lymphopenia.
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- History of acquired or inherited immune deficiency syndrome, including leukopenia.
- History of severe untreated chronic obstructive sleep apnea.
- FVC less than 50% predicted at screening.
- 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.
- 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.
- Clinically significant history of cardiac, oncologic, hepatic, or renal dysfunction, or other medically significant illness.
- The presence of any immunologic or autoimmune disease
- Severe cardiac dysfunction defined clinically, or as a left ventricular ejection fraction less than 40% of predicted or abnormal EKG findings.
Trial locations and contacts
1 site in 1 country.
United States1 site
Methodist Neurological Institute
Houston, Texas, 77030
About this study
Official title: Expansion and Infusion of T-Regulatory Cells in Amyotrophic Lateral Sclerosis
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.
Read the detailed description
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.
- Conditions
- ALS (Amyotrophic Lateral Sclerosis)
- Being tested
- Autologous T-regulatory lymphocytes, Interleukin-2
- Keywords
- ALS, T-Regulatory Cells
- Medical subject headings
- Amyotrophic Lateral Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Autologous T-regulatory lymphocytesBiological
intravenous administration of Autologous T-regulatory lymphocytes at a dose of 1x10 to the sixth /kg.
Interleukin-2Biological
Also called IL-2
Subcutaneous Interleukin-2 at a dose of 2x10 to the fifth IU/m2, three times a week.
| Study group | Role | What they receive |
|---|---|---|
| Treatment arm | Experimental | 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. Receives: Biological: Autologous T-regulatory lymphocytes; Biological: Interleukin-2 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Adverse events related to Treg infusions at Baseline to up to two years or study participation, whichever is occurs first.
Secondary outcomes (5)
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).
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline to 3 months post-treatment for a total of two years from baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Aug 2017
- Study start16 May 2016
- Primary completion5 Jan 2018
- Study completion10 Apr 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for ALS (Amyotrophic Lateral Sclerosis)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Autologous infusion of expanded T-regulatory lymphocytes during early and late phases of ALS disease in patients with varying rates of disease progression.
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Methodist Hospital Research Institute
- Sponsor type
- University, hospital or other
- Collaborators
- M.D. Anderson Cancer Center
- Responsible party
- Sponsor
- Investigators
- Stanley H Appel, MD, Principal investigator, Houston Methodist Neurological Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03241784
- Sponsor's protocol ID
- Pro00013616
- Status last verified
- Jun 2026
- First submitted
- 27 Jul 2017
- Last updated
- 17 Jun 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Expansion and Infusion of T-Regulatory Cells in Amyotrophic Lateral Sclerosis
- ClinicalTrials.gov ID
- NCT03241784
- Acronym / sponsor ID
- Pro00013616
- Conditions
- ALS (Amyotrophic Lateral Sclerosis)
- Keywords
- ALS, T-Regulatory Cells
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 3 participants (actual)
- Lead sponsor
- The Methodist Hospital Research InstituteUniversity, hospital or other
- Collaborators
- M.D. Anderson Cancer Center
- Study start
- 16 May 2016 (actual)
- Primary completion
- 5 Jan 2018 (actual)
- Study completion
- 10 Apr 2018 (actual)
- First posted
- 7 Aug 2017 (actual)
- Results
- Posted 17 Jun 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Autologous infusion of expanded T-regulatory lymphocytes during early and late phases of ALS disease in patients with varying rates of disease progression.
| Arm | Type | Receives |
|---|---|---|
| Treatment arm | Experimental | Biological: Autologous T-regulatory lymphocytes, Biological: Interleukin-2All 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Age 18 years or older.
- Sporadic or familial ALS diagnosed as possible, laboratory-supported probable, probable, or definite as defined by revised El Escorial criteria (Appendix 1).
- 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).
- Capable of providing informed consent and following trial procedures.
- Geographically accessible to the site.
Key exclusion criteria (14 listed)
- Prior use of cells therapies
- Concurrent use of other experimental ALS therapies
- Pregnant or breastfeeding or planning to become pregnant or planning a partner's pregnancy.
- Other unstable medical or psychiatric illness
- Known immune deficiency or history of lymphoma or leukemia
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Autologous T-regulatory lymphocytesintravenous administration of Autologous T-regulatory lymphocytes at a dose of 1x10 to the sixth /kg. | Biological | Treatment arm |
| Interleukin-2Also: IL-2Subcutaneous Interleukin-2 at a dose of 2x10 to the fifth IU/m2, three times a week. | Biological | Treatment arm |
Primary outcome
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).
Time frame: Adverse events related to Treg infusions at Baseline to up to two years or study participation, whichever is occurs first.
Adverse events and serious adverse events related to Treg infusions were monitored throughout the study.
5 secondary outcomes
Appel ALS (AALS) Scale/Grading
Time frame: Baseline and at week 15
ALSFRS-R (Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised)
Time frame: Baseline to week 15
T-Regulatory Cells
Time frame: Mean and standard deviation represent the average of baseline and 3-month assessments.
Treg Suppression
Time frame: Baseline to 3 months post treatment for a total of two years from baseline
T Helper Cells Type 1 (Th1) Lymphocytes
Time frame: Baseline to 3 months post-treatment for a total of two years from baseline
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jun 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stanley H Appel, MD principal investigator
Houston Methodist Neurological Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Autologous T-regulatory lymphocytes and Interleukin-2 in people with ALS (Amyotrophic Lateral Sclerosis), run by The Methodist Hospital Research Institute at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Jun 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). (time frame: Adverse events related to Treg infusions at Baseline to up to two years or study participation, whichever is occurs first.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jun 2026; AzTrials last refreshed its copy on 26 Oct 2026.