A Dose-escalation Safety Trial for Intrathecal Autologous Mesenchymal Stem Cell Therapy in Amyotrophic Lateral Sclerosis

Amyotrophic Lateral Sclerosis Clinical Trial

Official title:

A Dose-escalation Safety Trial for Intrathecal Autologous Mesenchymal Stem Cell Therapy in Amyotrophic Lateral Sclerosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01609283
• Other study ID #: 11-008415
• Status: Completed
• Phase: Phase 1
• Start date: May 2012
• Est. completion date: January 31, 2019

Study information

• Verified date: August 2019
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 27
• Est. completion date: January 31, 2019
• Est. primary completion date: January 31, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Motor Neuron Disease
• Sclerosis

Intervention

Biological:
• autologous mesenchymal stem cells
There will be five treatment groups of up to five 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 one month. Intrathecal injections into new subjects will be timed so that there is a minimum of one week between subject injections. The cell dose per group is as follows: Group 1: single intrathecal dose of 1 x 107 cells Group 2: single intrathecal dose of 5 x 107 cells Group 3: one intrathecal dose of 5 x 107 cells followed one month later by a second intrathecal dose of 5 x 107 cells Group 4: single intrathecal dose of 1 x 108 cells Group 5: one intrathecal dose of 1 x 108 cells followed one month later by a second intrathecal dose of 1 x 108 cells

Locations

Country	Name	City	State
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Mayo Clinic

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of patients with dose-limiting toxicities		baseline -2 years after completion of the final infusion
Secondary	Number of patients with adverse events		baseline -2 years after completion of the final infusion
Secondary	Change in serum sedimentation rate		baseline, 2 years after completion of the final infusion
Secondary	Change in C-reactive protein levels		baseline, 2 years after completion of the final infusion
Secondary	Change in complete blood counts		baseline, 2 years after completion of the final infusion
Secondary	Change in total nucleated cell count in cerebrospinal fluid (CSF)		baseline, 2 years after completion of the final infusion
Secondary	Change in protein level in cerebrospinal fluid (CSF)		baseline, 2 years after completion of the final infusion
Secondary	Number of patients with presence of cancer cells in their cerebrospinal fluid (CSF)		baseline -2 years after completion of the final infusion

External Links

•   Mayo Clinic Clinical Trials