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ALS Clinical Research Update
There are hundreds of scientists and doctors working hard to discover treatments for ALS. |
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News and Announcements
Congratulations to the NEALS Exercise Trial for Enrolling its First Participant!! How can exercise be combined with other treatments? Standard of care has been considered to be stretching and range of motion exercises; there has been little, if any, research into other forms of exercise in ALS patients. In this pilot study, 60 participants with ALS will be assigned to treatment in 1 of 3 arms: resistance exercise, endurance exercise, or stretching and range of motion exercise. Researchers are looking to learn about which is safe and tolerable for patients with ALS. The trial will enroll at four locations: Johns Hopkins University, Massachusetts General Hospital, Carolinas Medical Center, and Washington University in St. Louis, Missouri.
Upcoming NEALS Trial of Nuedexta
Nuedexta is a drug approved by the FDA for improving emotional lability in ALS and other disorders. Based on patient experience, a new NEALS trial will be starting soon to evaluate whether this drug improves bulbar functions such as swallowing and speaking. Information regarding inclusion criteria and study sites will be posted on the NEALS website when available. Study rationale will be discussed in an upcoming webinar:
Determining the effect of Nuedexta on speech and swallowing in ALS: A Multicenter Trial
June 5th, 2012
4pm-5pm EST
Richard Smith, MD (Center for Neurological Study)
Jeremy Shefner, MD, PhD (SUNY Upstate Medical Center)
ALS Association/NEALS PALS Webinars Series
NEALS offers live, online seminars (or "webinars") for people with ALS and other motor neuron disease. Experts explain the scientific rational and design of current ALS clinical research. Our webinars also offer participants the opportunity to ask questions directly to the experts running trials. Below is the information for our upcoming ALS Association/NEALS Patient Webinar:
Upper Motor Neuron Disease Research
July 2nd, 2012
3-3:45pm EST
Hiroshi Mitsumoto, MD (Columbia University)
Nazem Atassi, MD, MMSc (Massachusetts General Hospital, Harvard Medical School)
Neuralstem Announces Safety Results of First Twelve Participants
The first published results from an early-stage clinical trial show that spinal cord stem cells can be delivered safely into the spines of patients with the condition commonly known as Lou Gehrig's disease, opening the door for further research on this innovative approach. In a paper published online ahead of print publication in the peer-reviewed journal Stem Cells, a team from the University of Michigan, Emory University and study sponsor Neuralstem, Inc. report the results from 12 patients who took part in a study being conducted at Emory. Read more. |
NEALS at the 2012 Annual American Academy of Neurology Meeting
NEALS was represented at the annual AAN Meeting in New Orleans. A number of platform and poster presentations featured NEALS-affiliated research.
Presentations
A Study to Evaluate Safety and Tolerability of Repeated Doses of CK-2017357 (CK-357) in Patients with Amyotrophic Lateral Sclerosis
An oral presentation by Dr. Jeremy Shefner included data from Part B of a two-part, randomized, double-blind, placebo-controlled, multiple dose, safety, tolerability, pharmacokinetic and pharmacodynamic clinical trial of CK-2017357. CK-2017357 appeared to be safe and well-tolerated dosed daily at 125 mg, 250 mg, and 375 mg for two weeks; encouraging trends were observed in the Amyotrophic Lateral Sclerosis Functional Rating Scale (Revised) (ALSFRS-R), which assesses the impact of ALS on activities of daily living. Part B was identical to Part A of the trial, with the exception that all patients received Riluzole at a reduced dose of 50mg daily for 14 days with CK-2017357 or placebo.
Jeremy Shefner, Syracuse, NY, Richard Barohn, Kansas City, KS, Kevin Boylan, Jacksonville, FL, Deborah Bradshaw, Syracuse, NY, Benjamin Brooks, Charlotte, NC, Terry Heiman-Patterson, Radnor, PA, Jonathan Katz, San Francisco, CA, Nicholas Maragakis, Baltimore, MD, Hiroshi Mitsumoto, New York, NY, Alan Pestronk, Saint Louis, MO, Zachary Simmons, Hershey, PA, Andrew Wolff, Jacqueline Lee, Jean Masonek, Drew Jones , Lisa Meng, Jesse Cedarbaum, South San Francisco, CA
Electrical Impedance Myography as a Biomarker to Assess ALS Progression
Standard approaches to measuring disease progression are limited and include the ALS Functional Rating Scale-revised (ALSFRS-R) and handheld dynamometry. Dr. Seward Rutkove presented on electrical impedance myography's (EIM's) potential superiority for the detection of ALS progression over short periods of time while still correlating with a meaningful measure: survival.
Seward Rutkove, Boston, MA, James Caress, Michael Cartwright, Winston-Salem, NC, Ted Burns, Judy Warder, Charlottesville, VA, William David, Namita Goyal, Boston, MA, Nicholas Maragakis, Lora Clawson, Baltimore, MD, Michael Benatar, Miami, FL, Sharon Usher, Atlanta, GA, Khema Sharma, Miami, FL, Shiva Gautam, Pushpa Narayanaswami, Elizabeth Raynor, Boston, MA , Mary Lou Watson, Jeremy Shefner, Syracuse, NY
The EMPOWER Study: Design, Methodology and Baseline Features of the First Phase III Clinical Trial of Dexpramipexole for Patients with ALS
The purpose of EMPOWER, a Phase III, randomized, double-blind, placebo-controlled efficacy trial, is to investigate whether dexpramipexole (150 mg twice daily) is safe and effective in the treatment of ALS. A presentation was given to describe the design and baseline characteristics of EMPOWER. Eighty-one centers in 11 countries are participating in EMPOWER. Enrollment is complete, with 943 patients having been randomized. Results are expected in late 2012.
Merit Cudkowicz, Charlestown, MA, Leonard Van den Berg, Utrecht, Netherlands, Michael Bozik, Evan Ingersoll, Pittsburgh, PA, Alex Coppell, Berkshire, MA, United Kingdom, Wildon R. Farwell, Yingwen Dong, Douglas Kerr, Cambridge, MA
Timothy Miller, Saint Louis, MO, Richard Smith, La Jolla, CA, Alan Pestronk, Saint Louis, MO, William David, Boston, MA, Jeffrey Rothstein, Baltimore, MD, Ericka Simpson, Houston, TX, Patricia Andres, Reading, MA, Katy Mahoney, Charlestown, MA, Peggy Allred, St. Louis, MO, Katie Alexander, Kathie Bishop, Carlsbad, David Schoenfeld, Boston, MA, Erin Macklin, Charlestown, Daniel Norris, CA, C. Bennett, Carlsbad, CA , Merit Cudkowicz, Charlestown, MA
Posters
A Study to Evaluate Safety and Tolerability of CK-2017357 (CK-357) in Patients with Amyotrophic Lateral Sclerosis Using a Twice-Daily, Dose-Titration Regimen
Dr. Jeremy Shefner presented a poster with summarized data from a Phase II clinical trial evaluating safety and tolerability of CK-2017357 to determine if the total daily dose could be increased from 375 mg once daily to 250mg twice daily in patients with ALS.
CK-2017357, or placebo, was administered for 21 days using a twice-daily dose titration regime, with doses totaling 250 mg, 375 mg, and 500 mg daily. Doses were increased every seven days. Results indicate CK-2017357 was generally safe and well-tolerated and that the majority of patients could be titrated successfully to a dose level of 250 mg twice daily.
Jeremy Shefner, Syracuse, NY, Jinsy Andrews, Tappan, NY, Richard Bedlack, Durham, NC, James Berry, Charlestown, MA, Kimberly Goslin, Portland, OR, Carlayne Jackson, San Antonio, TX, John Kissel, Columbus, OH, Dale Lange, New York, NY, Jonathan Licht, San Diego, CA, Tahseen Mozaffar, Orange, CA, Alan Pestronk, Saint Louis, MO, Jeffrey Rosenfeld, Fresno, CA, Andrew Wolff, Jacqueline Lee, Jean Masonek , Drew Jones, Lisa Meng, Jesse Cedarbaum, South San Francisco, CA
Platform for Clinical Trials Data Integration and Sharing as a Unique Industry, Academic, and Foundation Collaboration Resource in ALS Research
NEALS is partnering with Prize4Life to develop the PRO-ACT Database, an ALS clinical trial record database comprised of data collected from Phase II and III trials conducted over the past 20 years. Through funding from the ALS Therapy Alliance, this database will be the largest ALS patient record dataset assembled to date and will mark not only the first time that much of this data are available to the research community, but the first time this data will be accessible as one comprehensive resource. The PRO-ACT Database will:
* contain over 6500 de-identified patient data records from completed industry trials (including both placebo and drug data);
* incorporate clinical trial data from six publicly-funded NEALS clinical trials (approximately 1000 records); and
* include at least three other academic clinical trial datasets.
Patients' clinical data, regardless of the outcome of the trial in which they were enrolled, provide researchers with valuable insight to begin to better understand ALS and its mechanisms. Just as pooled trial datasets have been important for other multifaceted diseases, such as Alzheimer's Disease, collaborators on the PRO-ACT Database hope it will serve as a valuable tool to address issues in the ALS field pertaining to clinical trial design and biomarkers, amongst others. A subset of data can be expected to be made publicly available by this summer, and the full dataset is scheduled to launch publicly in December of this year.
Alexander Sherman, Charlestown, MA, Melanie Leitner, Cambridge, MA, Ervin Sinani, Igor Katsovskiy, Merit Cudkowicz, Charlestown, MA
Early diagnosis of ALS is essential to allow earlier interventions to reduce the cost of multiple testing, and reduce patient's stress due to the prolonged uncertainty about the diagnosis. Despite the increased knowledge and awareness of ALS, the time from ALS symptom onset to diagnosis remains to be approximately 12 months. This retrospective study, conducted through a cohort of patients at Massachusetts General Hospital, sought to determine early presenting symptoms and signs, specialists seen, and alternative diagnoses given before ALS diagnosis was confirmed. The researchers concluded that it takes approximately 12 months from symptom onset to suspect the diagnosis of ALS and refer patients to ALS clinics. Once patients are evaluated by an ALS specialist, confirming the diagnosis occurs quickly with in 2 months. Patients visit an average of 3 specialties before confirming ALS diagnosis and approximately half of these visits resulted in no diagnosis. The most common early alternative diagnoses given to people with ALS were neuropathies, spine problems, strokes, and neuromuscular junction disorders.
Nazem Atassi, Alexandra Lee, Judith Chang, Charlestown, MA, Eric Macklin, Boston, MA, Merit Cudkowicz, Charlestown, MA
Dexpramipexole Effects on Functional Decline in ALS Patients in a Phase II Study: Subgroup Analysis of Demographic and Clinical Characteristics
A post-hoc analysis was conducted from the data of a two-part, Phase II study of oral dexpramipexole, in which dexpramipexole was well tolerated for up to 9 months in ALS patients, to explore potential differential treatment effects in a variety of patient subgroups. Results indicated that, regardless of baseline demographic and clinical characteristics, 300mg of dexpramipexole was slightly more beneficial than was 50mg of dexpramipexole on functional decline.
Stacy Rudnicki, Little Rock, AR, James Berry, Charlestown, MA, Evan Ingersoll, Donald Archibald, Pittsburgh, PA, Merit Cudkowicz, Charlestown, MA, Douglas Kerr, Yingwen Dong, Cambridge, MA
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Scientific Advisory Board Roundtable
The NEALS Scientific Advisory Board (SAB) convened in Boston, MA this past April to discuss current scientific developments and new directions for the field of ALS research. Twenty-three researchers from academic institutions, ALS foundations, and biopharmaceutical companies attended the meeting which was led by NEALS SAB Co-Chairs, Robert Brown, DPhil, MD (University of Massachusetts) and Jeffery Rothstein, MD, PhD (Johns Hopkins). The objective of the round-table discussion was to evaluate potential therapies for the treatment of ALS and UMND, including assessing ready and near-ready therapeutic candidates for future clinical trials and reviewing ongoing NEALS trials. The meeting built upon work completed at last year's round-table discussion and expanded the list of compounds of interest to NEALS.
The SAB is responsible for advising the NEALS Executive Committee and NEALS members about the scientific basis of NEALS research activities. This includes but is not limited to the development, conduct, analysis, and publication of NEALS trials. The SAB holds a day-long roundtable once a year, generally in the spring.
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Enrolling ALS Trials
The following are NEALS trials that are currently enrolling new participants.
Phase II Trial
Phase II High Fat/High Calorie Trial
A phase II nutritional diet trial looking at safety, tolerability, and preliminary efficacy. The trial is investigating the ideal amount and type of calories to be consumed by ALS patients daily. Participants must be currently tolerating tube feedings through the use of either a g-tube or j-tube. Participants will be randomly assigned to consume one of three diets: high fat and high calorie, high calorie, or normal diet. The trial consists of five in-person clinic visits and four telephonic visits over five months: four months of tube feeds with an additional month for follow-up. This trial is currently enrolling at 12 sites throughout the United States.
Stem Cell Trials
Neural Stem Cell Transplantation
Neuralstem's ongoing Phase I trial is designed to determine safety of human spinal cord stem cells transplantation into ALS patients. The trial is enrolling patients by invitation; participants must live within close proximity to Atlanta, GA. The first twelve patients were all transplanted in the lumbar, or lower back, region of the spine. Published results show that spinal cord stem cells can be delivered safely into the lumbar region. Three patients have now been treated with stem cell injections into the cervical spinal cord (in the neck), targeting the motor neurons that are responsible for respiratory function. Brainstorm Stem Cell Trial
Brainstorm Cell Therapeutics is performing a Phase I/II clinical trial at the Hadassah Medical Organization in Israel, and is currently enrolling ALS participants in a trial of autologous transplantation of Mesenchymal Stromal Stem cells secreting Neurotrophic factors (MSC-NTF), taken from the patient's own bone marrow. The cells are delivered into the muscles or into the spinal fluid.
Familial ALS Trial
Arimoclomol in SOD1 Positive Familial ALS
An amplifier of heat-shock protein, Arimoclomol is being investigated in a phase II/III randomized, double-blind, placebo-controlled trial in patients with SOD1 positive familial ALS. Researchers are assessing safety, tolerability, and efficacy of Arimoclomol and hypothesize that it will slow disease progression. This trial is currently enrolling 80 participants at two sites: the University of Miami and Massachusetts General Hospital.
Biomarkers Study
A Multicenter Study for the Discovery and Validation of Biomarkers in ALS
This biomarkers study is recruiting participants at NEALS sites in Boston MA, Worcester MA, Pittsburgh PA, Atlanta GA, Jacksonville FL, and Phoenix AZ. Blood samples and cerebrospinal fluid (CSF) from patients with ALS will be collected. Through comparison of these samples, the researchers will learn more about the underlying cause of ALS, as well as find unique biological markers, which could be used to diagnose ALS more quickly and develop new therapies.
For a full list of enrolling trials, go here. |
Enrollment Closures
Selection Trial of High Dosage Creatine and Two Dosages of Tamoxifen
The Phase II Selection Trial of High Dosage Creatine and Two Dosages of Tamoxifen has recently completed enrollment. Sixty subjects have been enrolled at 9 NEALS sites across the US. Each participant will take one active study drug (creatine 30gm, tamoxifen 40mg, or tamoxifen 80mg) and one placebo for 38 weeks. This trial has a unique design which allows selecting the most promising treatment to be tested in a future larger trial. Trial results are anticipated to be announced in the beginning of 2013.
For more information on the Selection Trial, click here. Questions can be directed to Kate Jackson at kjackson13@partners.org or 617-724-3871.
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Researcher Highlight
Robert Bowser, PhD, serves as Director of the Gregory W. Fulton ALS and Neuromuscular Research Center at Barrow Neurological Institute ALS Neuromuscular Research Center; Co-Chair of the NEALS Biofluid Repository Committee; and Professor, Divisions of Neurology and Neurobiology.
For the past 20 years, Robert Bowser, PhD, has been studying how the regulation of gene expression is involved in neurodegenerative diseases. Having first started his scientific career researching Alzheimer's disease... Click here to read more.
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ALS Association/ NEALS Trial Expert
Devon Punch is the "ALS Association/NEALS Clinical Trial Expert." She is available to help people with motor neuron disease and their caregivers navigate the NEALS website and answer questions about clinical research during normal business hours eastern standard time. ALS Trial Expert (877) 458-0631 alstrials@partners.org |
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