ALS, Amyotrophic Lateral Sclerosis
Conditions
Brief summary
The purpose of this study is to determine the safety and efficacy of intrathecal treatment delivered to the cerebrospinal fluid (CSF) of mesenchymal stem cells in ALS patients every 3 months for a total of 4 injections over 12 months. Mesenchymal stem cells (MSCs) are a type of stem cell that can be grown into a number of different kinds of cells. In this study, MSCs will be taken from the subject's body fat and grown. CSF is the fluid surrounding the spine. The use of mesenchymal stem cells is considered investigational, which means it has not been approved by the Food and Drug Administration (FDA) for routine clinical use. However, the FDA has allowed the use of mesenchymal stem cells in this research study.
Detailed description
The Goal of the Proposed Study is to perform an open label, 60 subject, Phase II multi-site clinical trial to investigate the safety and efficacy of intrathecal treatment of aaMSCs in ALS. Patients will be treated with 10-100 million aaMSCs every 3 months for a total of 4 intrathecal injections over 12 months. Reduced dose treatments will be allowed based on specific adverse events. Multiple biomarkers will be tracked throughout the clinical trial and correlated with response to treatment. This study was initially performed at Mayo Clinic in Rochester and subsequently expanded to the two other Mayo Clinic sites in Arizona and Florida. All biopsies and stem cell injections take place at Mayo Clinic Rochester, regardless of where the subject initially enrolls into the study.
Interventions
The investigational product consists of autologous adipose-derived Mesenchymal Stromal Cells (MSCs), suspended in 5-10 mL Lactated Ringer's. The MSC are provided in a sterile syringe labelled with appropriate patient and product identifiers ready for intrathecal injection.
Sponsors
Mayo Clinic
State of Minnesota Regenerative Medicine Minnesota
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* All patients will have ALS diagnosed as possible, laboratory-supported probable, probable, or definite as defined by the World Federation of Neurology criteria for the diagnosis of ALS. * Examination and neurophysiological testing confirm a pure motor syndrome compatible with the diagnosis of ALS. All other possible causes of weakness have been excluded by extensive investigations. * Age greater than 18 years, if female, must be post-menopausal, had a hysterectomy, or agree to two forms of birth control. * Permanent resident or citizen of the United States. * Geographic accessibility to the study site and willingness and ability to comply with follow-up. * History of a chronic onset of a progressive motor weakness of less than two years duration. * Subjects must be taking a stable dose of riluzole for at least 30 days prior to enrolment or not be on riluzole, and not have been on it for at least 30 days prior to enrolment (riluzole-naïve subjects are permitted in the study). * Subjects must be taking a stable dose of oral Radicava® (edaravone) for at least 30 days prior to enrolment or not be on oral Radicava® (edaravone), and not have been on it for at least 30 days prior to enrolment (edaravone-naïve subjects are permitted in the study). * Able to comply with protocol requirements, including MRI testing. * Can provide written informed consent.
Exclusion criteria
* Use of Radicava® (edaravone) within 30 days of screening or intent to use Radicava® at any time during the course of the study including the follow up period. * Any clinically significant medical condition (e.g., within six months of baseline, had myocardial infarction, angina pectoris, and/or congestive heart failure) that, in the opinion of the investigator, would compromise the safety of patient. * Pulmonary Slow Vital Capacity (SVC) less than 65% of predicted for age, gender, and body type. * Autoimmunity, including Crohn's disease or rheumatoid arthritis * Current use of immunosuppressant medication or use of such medication within 4 weeks of Screening visit (Visit 1). * Malignancy 5 years prior to enrollment, including melanoma,with the exception of localized skin cancers (with no evidence of metastasis, significant invasion, or re-occurrence within three years of baseline). * Active systemic or local infection near the lumbar puncture site. * Inability to lie flat for the duration of intrathecal cell transplantation, or inability to tolerate study procedures for any other reason. * Other active systemic disease as defined by laboratory abnormalities delineated in Appendix IV. * Use of herbal medications, nutritional supplements or other unapproved drugs or investigational medicinal products being used or studied for the treatment of ALS. * Unwilling to forgo initiating the use of any new supplements during participation in the study. * Enrolled in an investigational drug trial within 30 days of baseline visit * Prior stem cell therapy for a neurological disease * Kokmen Short Test of Mental Status score \<32 * Presence of a tracheostomy * Ventilator dependent * Pregnancy * Men or women of childbearing potential who are unwilling to employ adequate contraception * Chronic low back pain requiring invasive procedures (i.e. epidural injections or lumbar spine surgery)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events | 12-months | The number of adverse events experienced by subjects |
| Unexpected Severe Adverse Events | 12-months | The number of unexpected severe adverse events experienced by subjects |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Slope of ALS Functional Rating Scale - Revised (ALSFRS-R) | baseline, approximately 1 year | The ALSFRS-R includes 12 questions. Each task is rated on a five-point scale from 0 = can't do, to 4 = normal ability. Individual item scores are summed to produce a reported score of between 0=worst and 48=best. The change in slope is the rate at which a patient's functional ability declines over time, as measured by the change in the ALFSFRS score over 1 year. A steeper slope signifies a faster decline in function. A negative change in slope indicates a decline in function and positive change in slope indicates an improvement in function. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORNathan P Staff, MD, PhD
Mayo Clinic
PRINCIPAL_INVESTIGATORAnthony J Windebank, MD
Mayo Clinic
Participant flow
Pre-assignment details
75 participants signed the informed consent form, however nine participants screened failed prior to being randomized.
Participants by arm
| Arm | Count |
|---|---|
| Mesenchymal Stromal Cells Autologous Adipose-derived Mesenchymal Stromal Cells (aaMSCs) were administered intrathecally at a single dose in a volume of 5-10 mL, all patients received 5 x 10\^7 intrathecal aaMSCs at the first injection (Visit 4). Subsequent doses may be reduced to 1 x 10\^7 or increased to 1 x 10\^8, based on Dose Modification Rules.
Autologous Adipose-derived Mesenchymal Stromal Cells: The investigational product consists of autologous adipose-derived Mesenchymal Stromal Cells (MSCs), suspended in 5-10 mL Lactated Ringer's. The MSC were provided in a sterile syringe labelled with appropriate patient and product identifiers ready for intrathecal injection. | 57 |
| Total | 57 |
Baseline characteristics
| Characteristic | Mesenchymal Stromal Cells |
|---|---|
| Age, Continuous | 56 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 55 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 55 Participants |
| Region of Enrollment United States | 57 participants |
| Sex: Female, Male Female | 17 Participants |
| Sex: Female, Male Male | 40 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 4 / 57 |
| other Total, other adverse events | 56 / 57 |
| serious Total, serious adverse events | 26 / 57 |
Outcome results
Primary
Adverse Events
The number of adverse events experienced by subjects
Time frame: 12-months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mesenchymal Stromal Cells | Adverse Events | 668 Number of Adverse Events |
Primary
Unexpected Severe Adverse Events
The number of unexpected severe adverse events experienced by subjects
Time frame: 12-months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mesenchymal Stromal Cells | Unexpected Severe Adverse Events | 41 Number of unexpected severe adverse eve |
Secondary
Change in Slope of ALS Functional Rating Scale - Revised (ALSFRS-R)
The ALSFRS-R includes 12 questions. Each task is rated on a five-point scale from 0 = can't do, to 4 = normal ability. Individual item scores are summed to produce a reported score of between 0=worst and 48=best. The change in slope is the rate at which a patient's functional ability declines over time, as measured by the change in the ALFSFRS score over 1 year. A steeper slope signifies a faster decline in function. A negative change in slope indicates a decline in function and positive change in slope indicates an improvement in function.
Time frame: baseline, approximately 1 year
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Mesenchymal Stromal Cells | Change in Slope of ALS Functional Rating Scale - Revised (ALSFRS-R) | -0.11 Score on a scale/year |
p-value: 0.38Wilcoxon (Mann-Whitney)