A Novel Immunosuppression Intervention for the Treatment of Amyotrophic Lateral Sclerosis (ALS)
Study Purpose:
This is a multicenter, 15-month study evaluating the effect of immunosuppression treatment on the rate of change on the ALS Functional Rating Scale (Revised) (ALSFRS-R) score in 30 subjects with Amyotrophic Lateral Sclerosis (ALS)
Disease:
Amyotrophic Lateral Sclerosis (ALS), Familial ALS, Sporadic ALSStudy Type:
Interventional TrialStudy Category:
Drug TrialStudy Status:
Not enrollingPhase:
Phase IIStudy Chair(s)/Principal Investigator(s):
Jonathan Glass, MD (Emory University)
Christina Fournier, MD (Emory University)
Clinicaltrials.gov ID (11 digit #):
NCT01884571Neals Affiliated?
YesCoordinating Center Contact Information
Massachusetts General HospitalMichelle McGovern / .(JavaScript must be enabled to view this email address) / 617-723-1618
.(JavaScript must be enabled to view this email address) 165 Cambridge Street
Boston, Massachusetts 02114 United States
Full Study Summary:
In an ongoing safety trial of neural stem cell injections into the spinal cord of patients with ALS at Emory University, Atlanta, Georgia, one patient has demonstrated clear improvement by objective clinical and electrophysiological measures, a finding that is unheard of in patients with ALS.
This patient had an improvement in ALSFRS-R by 1.4 points per month. In 826 historical controls from the Northeast ALS Consortium (NEALS) and the Western ALS Consortium (WALS) database where ALSFRS-R was documented at 2 or more visits, there have been no patients that have shown improvement in ALSFRS as seen in this case. Additionally, 5 patients in the stem cell trial who were not on mechanical ventilators at the time of surgery seem to have very slow disease progression as compared to the expectation from current understanding of typical disease course. This observation raises consideration for a disease-modifying effect of the novel immunosuppression regimen used in this trial. Also, given that ALS is clinically an extraordinarily heterogeneous disease, the diagnosis of ALS may represent a group of phenotypically similar but pathogenically variable disorders. It is possible that there exists a subset of patients with an immune-responsive ALS subtype that has not been previously recognized.
Recent studies have furthered the understanding of the immune mechanisms that contribute to ALS progression. Microglia and lymphocytes have both neurotoxic and neuroprotective functions depending on activation states and physiologic conditions within the nervous system. Therefore, targeted immunotherapies that proportionally suppress neurotoxic immune elements, while sparing or promoting protective elements, seemingly have more potential to modify disease course in ALS than previously tested regimens. It is postulated that the immunosuppression treatment given to the stem cell patients may have exhibited neuroprotective effects by favorably promoting the ratio of regulatory T cells and other protective immune mediators in relation to neurotoxic immune modulators. It is hoped that this trial will optimize the chance of replicating these findings and allow the learning more about the complex changes that occur within the immune system in patients with ALS before and after treatment with an immunosuppression regimen.
The primary objective of this study is to assess the clinical response rate of a novel immunosuppression regimen in a subset of ALS patients.
The primary outcome measure will be rate of change of ALSFRS-R. A clinical response will be defined as a rate of change of ALSFRS-R of +6 points over a 6 month period (mean of change of +1 point per month).
Secondary outcome measures will include slow vital capacity (SVC), grip strength, and hand held dynamometry (HHD). The change in rate of progression in clinical measures will be monitored to look for a potential disease-modifying effect of the immunosuppression regimen.
Approximately 33 eligible subjects with ALS will be recruited from 3 centers in the US.
Study Sponsor:
The ALS Association, ALS Therapy Alliance (ATA) and Northeast ALS (NEALS) ConsortiumParticipant Duration:
Subjects will undergo monthly clinical evaluations for three (3) months prior to treatment to document course of disease. They will then be on a six (6) month treatment regimen of immunosuppression with monthly visits to monitor for safety and to check clinical measurements. Safety monitoring and clinical measures will continue for six (6) months post-treatment. In addition, blood and cerebrospinal fluid will be collected prior, during, and post-treatment in order to characterize markers of the subject™s immune system and further the understanding of the immune factors that contribute to disease progression in ALS.