Clinical trial NCT01609283: A Dose-escalation Safety Trial for Intrathecal Autologous Mesenchymal Stem Cell Therapy in Amyotrophic Lateral Sclerosis
Official title: A Dose-escalation Safety Trial for Intrathecal Autologous Mesenchymal Stem Cell Therapy in Amyotrophic Lateral Sclerosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Amyotrophic Lateral Sclerosis
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
First posted: 2012-05-31
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine determine the safety of intraspinal delivery of mesenchymal stem cells (MSCs) to the cerebral spinal fluid of patients with Amyotrophic Lateral Sclerosis (ALS) using a dose-escalation study.

Detailed description: The primary objective of this study is to determine the safety of intrathecal delivery of autologous mesenchymal stem cells (MSCs) to the cerebrospinal fluid (CSF) of patients with ALS using a dose-escalation study. The trial will include 25 adult, non-ventilator-dependent patients with clinically definite amyotrophic lateral sclerosis (ALS). Cells will be isolated from adipose tissue, expanded ex vivo and then, after \~8 weeks, intrathecal (IT) autologous delivery of MSCs will be performed. There will be 5 treatment groups of up to 5 patients each. Groups 1, 2, and 4 will receive a single dose of cells. Groups 3 and 5 will receive 2 doses of cells separated by 1 month. Groups will be completed sequentially so that patients will not be enrolled into the next treatment group until at least 3 patients in the preceding group have completed the treatment and 1 month of additional observation without significant toxicity. All patients will be followed on a regular basis until death or for a minimum of 2 years after completion of the final infusion. Initial clinical follow-up will be weekly with scheduled blood, CSF and magnetic resonance imaging (MRI) evaluations. After 1 month, patients will have clinical evaluations at 3 month intervals, or earlier if indicated by clinical status.

Addendum: Five subjects from the Group 5 dosing level will received additional injections of MSCs in an extension of the original study, if tolerated.

Eligibility criteria: Inclusion Criteria:

* All patients must have clinically-defined ALS as defined by the World Federation of Neurology criteria
* Age greater than 18 years
* If female, must be post-menopausal or had a hysterectomy
* Permanent resident or citizen of the United States
* History of a chronic onset of a progressive motor weakness of greater than one year, but less than two years duration
* Must have vital capacity greater than 65% of predicated for age, gender, and body type
* Able to comply with protocol requirements, including MRI testing
* Can provide written informed consent

Exclusion Criteria:

* 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.
* Autoimmunity, including Crohn's disease, rheumatoid arthritis, psoriasis
* Malignancy including melanoma with the exception of localized skin cancers (with no evidence of metastasis, significant invasion, or re-occurrence within three years of baseline). Any other malignancy will not be allowed.
* Active systemic or local infection near the lumbar puncture site
* Other active systemic disease as defined by laboratory abnormalities
* Use of herbal medications or other unapproved drugs
* Enrolled in an investigational drug trial within 30 days of baseline visit
* Kokmen Short Test of Mental Status score \<32
* Beck's Depression Inventory score \>18
* Presence of a tracheostomy
* Ventilator dependent

Primary outcomes:
measure: Number of patients with dose-limiting toxicities
timeFrame: baseline -2 years after completion of the final infusion
Secondary outcomes:
measure: Number of patients with adverse events
timeFrame: baseline -2 years after completion of the final infusion
measure: Change in serum sedimentation rate
timeFrame: baseline, 2 years after completion of the final infusion
measure: Change in C-reactive protein levels
timeFrame: baseline, 2 years after completion of the final infusion
measure: Change in complete blood counts
timeFrame: baseline, 2 years after completion of the final infusion
measure: Change in total nucleated cell count in cerebrospinal fluid (CSF)
timeFrame: baseline, 2 years after completion of the final infusion
measure: Change in protein level in cerebrospinal fluid (CSF)
timeFrame: baseline, 2 years after completion of the final infusion
measure: Number of patients with presence of cancer cells in their cerebrospinal fluid (CSF)
timeFrame: baseline -2 years after completion of the final infusion
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Anthony Windebank, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Camilleri ET, Gustafson MP, Dudakovic A, Riester SM, Garces CG, Paradise CR, Takai H, Karperien M, Cool S, Sampen HJ, Larson AN, Qu W, Smith J, Dietz AB, van Wijnen AJ. Identification and validation of multiple cell surface markers of clinical-grade adipose-derived mesenchymal stromal cells as novel release criteria for good manufacturing practice-compliant production. Stem Cell Res Ther. 2016 Aug 11;7(1):107. doi: 10.1186/s13287-016-0370-8.