- In a semi-virtual trial involving 47 patients with amyotrophic lateral sclerosis (ALS), there was no evidence that lunasin slowed or reversed disease progression
- Lunasin did not significantly influence histone acetylation patterns in the blood
- Lunasin was associated with gastrointestinal side effects, including two cases of obstipation/fecal impaction requiring hospitalization that were considered possibly treatment-related
- The investigators were pleased with the logistical performance of the trial, which had the fastest enrollment rate in ALS history
In 2014, a television news story galvanized the community of patients and families affected by amyotrophic lateral sclerosis (ALS). It reported that a patient with lower-motor-neuron-predominant ALS had experienced dramatic improvement in his speech, swallowing and limb strength by using a regimen containing lunasin, a peptide derived from soy. The improvements were later independently validated.
Because of intense interest from patients, and because lunasin was not known to have any serious adverse effects, investigators led by Richard Bedlack, MD, PhD, at Duke University and Ghazaleh Sadri-Vakili, MS, PhD, director of the NeuroEpigenetics Laboratory in the Mass General Institute for Neurodegenerative Disease, conducted a pilot trial in ALS.
While the results of the trial were negative, the innovative design of the trial suggests ways to improve clinical research into ALS therapies. The trial design and results are described in Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration.
A Semi-Virtual Trial
To address patients' frustrations with common features of ALS trials, the investigators used broad inclusion criteria, used historical controls instead of a placebo group and made results available in real time. They also minimized travel burden by making the trial semi-virtual:
- In-person visits to the clinic were required only at enrollment, month one and month 12. These included training on using the ALS Functional Rating Scale-Revised (ALSFRS-R) and PatientsLikeMe.com
- Virtual visits were made at weeks two and three, then once per month for months 2–11. On PatientsLikeMe.com, patients entered their self-measured ALSFRS-R score and weight, along with ratings of perceived lunasin efficacy and side effects
- Telephone visits at weeks two and three continued the ALSFRS-R training and helped patients with the website
Study Population and Treatment
Forty-seven participants were evaluated, with no limitation on disease duration or breathing function. The average disease duration was longer than in most ALS trials (average 3.7 years, range, 0.5–13 years). Eight participants had feeding tubes, 20 used non-invasive ventilation and three had tracheostomies and used invasive ventilation. Most (60%) were on riluzole.
The investigators calculated each participant's pretreatment ALSFRS-R progression using their symptom onset date (when ALSFRS-R score was assumed to be 48) and the ALSFRS-R score at their first study visit. Drawing on its existing population of ALS patients, PatientsLikeMe matched each participant to three controls with similar pretreatment progression.
Participants were asked to take the same lunasin-containing products at the same dosages as the patient from the television report.
There was no significant difference between the participants and the 141 matched historical controls with regard to ALSFRS-R progression.
Most participants reported little or no effect of lunasin. No participant experienced ALS reversal, which was predefined as improvement of at least four ALSFRS-R points.
Lunasin has been reported to alter histone acetylation patterns. Therefore, the investigators used histone acetylation as a pharmacodynamic biomarker to determine the on-target effects of lunasin treatment. Changes in histone acetylation were measured in participants on lunasin, as well as five healthy controls and five ALS controls, had blood drawn at enrollment and month one. Overall, there was no significant effect of lunasin on acetylated histone H3 or H4.
Of 15 serious adverse events during the study, two cases of obstipation/fecal impaction requiring hospitalization were considered possibly related to lunasin. The most common non-serious adverse events attributed to lunasin were constipation (n=11) and fullness/early satiety (n=8). 32 participants lost an average of four pounds during the study.
This was the fastest-enrolling trial in ALS history at 9.1 participants per month, nearly five times higher than average. Participant retention (84% among survivors) and adherence were both judged to be excellent.
The investigators plan to use similar trial designs in future assessments of other alternative therapies, perhaps even without in-person visits. They recommend patient-centric features for all ALS trials, such as including patients on the study committee, minimizing burden through virtual visits and providing results to participants as quickly as possible in open access forums.
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