Trial investigators are actively seeking people with amyotrophic lateral sclerosis (ALS) to participate in a phase 2 clinical trial that will evaluate the effects of a five-drug treatment regimen used to suppress immune system activity.
The design of the trial is based on findings from a recently completed safety trial of injections of neural stem cells into the spinal cords of people with ALS. In that trial, one participant demonstrated signs of improvement, and in several other participants the rate of ALS disease progression appeared to slow — apparent effects that may have been due to protection of the nervous system by the immunosuppressant drugs. (Alternatively, the effects may be attributable to the stem cells, or to the combination of stem cells and the immunosuppressant regimen.) Immunosuppression was administered to the trial participants to prevent an unwanted immune response that could cause the body to reject the stem cells.
It's hoped the new trial will replicate the findings from the stem cell trial and increase understanding about the complex changes that occur within the immune system in people with ALS both before and after treatment to suppress the immune system. (A growing body of evidence suggests that changes in the immune system play a role in the ALS disease process.)
Trial findings could point the way toward therapies aimed at modifying the immune system by suppressing harmful or toxic changes and/or boosting changes that are protective.
Three trial sites
Study investigators expect to enroll approximately 30 people with ALS for the 15-month study, which will be conducted at three trial sites in the United States. Jonathan Glass and Christina Fournier, both at Emory University in Atlanta, are the principal investigators for the trial. Glass directs the MDA/ALS Center at Emory University School of Medicine, which also serves as an MDA ALS Clinical Research Network trial site.
Participants will be administered:
Basiliximab, tacrolimus and mycophenolate mofetil are immunosuppressant medications that decrease immune system activation. Side effects of these types of drug can include gastrointestinal problems, such as constipation, nausea, abdominal pain, vomiting and diarrhea; respiratory problems, such as shortness of breath and upper respiratory tract infection; cardiovascular disorders, such as high blood pressure; central and peripheral nervous system problems, such as headache and tremor; and psychiatric problems, such as insomnia. Other effects include high blood pressure, heart problems, and swelling of the lower legs, ankles and feet.
Methylprednisolone and prednisone are glucocorticoids, or corticosteroids, which are commonly used to reduce inflammation. Common side effects of these drugs include high blood sugar levels and fluid retention, insomnia and depression or anxiety. Long-term use can cause weight gain, a decrease in bone density, glaucoma and cataracts.
Note: Although the drugs used in the study may be available by prescription, their effects in ALS are unknown and they could cause serious side effects. MDA advises individuals not to use the drugs to treat ALS until their safety and efficacy have been proven in clinical trials.
The primary outcome measure to indicate a disease-modifying effect will be the rate of change of ALSFRS-R (ALS Functional Rating Scale — Revised), a widely used and validated measure of functional ability in ALS. Secondary outcome measures include slow vital capacity or SVC (the maximum volume of air that can be exhaled slowly after slow maximum inhalation) and grip strength. Blood and cerebrospinal fluid immune system markers also will be studied.
The trial is a project of the Northeast ALS Consortium (NEALS); MDA is not funding this trial.
For more information about the study, see Immunosuppression in Amyotrophic Lateral Sclerosis (ALS) (NIPALS2013) or enter NCT01884571 in the search box at ClinicalTrials.gov.
Prospective participants must:
Study sites are located at:
Massachusetts General Hospital, Boston
Contact: Owen O'Connor — (617) 726-5059, or firstname.lastname@example.org.
University of Massachusetts Medical School, Worcester, Mass.
Contact: Diane McKenna-Yasek — (508) 856-4697, or email@example.com
About Clinical Trials
A clinical trial is a test, in humans, of an experimental treatment. Although it's possible that benefit may be derived from participating in a clinical trial, it's also possible that no benefit, or even harm, may occur.