ALS (Amyotrophic Lateral Sclerosis)
Conditions
Brief summary
This is a 12-month, widely inclusive, largely virtual, single-center, open-label pilot trial utilizing a historical control group. Participants will receive a Lunasin regimen and will be asked to register for an account of PatientsLikeMe website, where after the initial in-clinic visit, they will be asked to enter specific data.
Detailed description
The primary hypothesis is that a supplement regimen containing Lunasin (referred to as the Lunasin regimen) can decrease the rate of ALSFRS-S progression by 50% relative to matched historic controls. ALS is a devastating motor neuron disease that causes rapidly progressive muscle weakness, disability and premature death. In spite of a large number of attempted ALS trials, there are no significant disease-modifying therapies for this condition. It was recently reported that a patient with a validated diagnosis of ALS, had experienced dramatic objective improvement in speech, swallowing and limb strength while taking a supplement regimen containing Lunasin. Several other patients with ALS have also reported improvement on this Lunasin regiment, though records were not obtainable to validate these. The Lunasin regimen will consist of: * LunaRich X Capsules * Reliv NOW - a mixture of 'vitamins, minerals and super-powered antioxidants' * Pro-Vantage - a mixture of 'soy protein, medium chain triglycerides, creatine, CoQ10 and supercharged amino acids' Dosages will be titrated up to target over the first 6 days. The subject will take the highest tolerated dosing for the remainder of the 12-month study. There are 3 in-clinic visits which occur at screening/baseline, Month 1 and Month 12. For Months 2-11, participants will make virtual visits by measuring their own ALSFRS-R score and weight and will record it in the PatientsLikeMe website. They will also self-report any perceived efficacy, compliance, adverse events and changes in concomitant medications.
Interventions
DRUGLunasin Regimen
LunaRich X Capsules, Reliv Now, ProVantage
OTHERHistorical control
Matched historical controls will be identified from the PatientsLikeMe database.
Sponsors
Richard Bedlack, M.D., Ph.D.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female, aged at least 18 years. * Sporadic or familial ALS diagnosed as possible, laboratory-supported probable, probable, or definite as defined by revised El Escorial criteria. * Patient is able to understand and express informed consent (in the opinion of the site investigator). * Patient has access to the Internet on a desktop computer, laptop, or tablet and has a working email address. * Patient or caregiver is willing and able to use a computer and enter data on a secure website. * Patient is able to read and write English. * Women must not be able to become pregnant (e.g., post-menopausal, surgically sterile, or using adequate birth control methods) for the duration of the study and three months after study completion. Adequate contraception includes: abstinence, hormonal contraception (oral contraception, implanted contraception, injected contraception or other hormonal contraception, for example patch or contraceptive ring), intrauterine device (IUD) in place for ≥ 3 months, barrier method in conjunction with spermicide, or another adequate method.
Exclusion criteria
* Patient is taking other experimental treatments for ALS. * Prior side effects from Lunasin. * Known soy allergy. * Patient has a medical or psychiatric illness that could in the investigator's opinion interfere with the patient's ability to participate in this study. * Pregnant women or women currently breastfeeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Revised ALS Functional Rating Scale (ALSFRS-R) | Screening/baseline - 12 months | ALSFRS-R is a quickly administered (five minute) ordinal rating scale used to determine patient's assessment of their capability and independence in 13 functional activities. All 13 activities are relevant in ALS. Each task is rated on a five-point scale from 0 = can't do, to 4 = normal ability, with a total score of 52 points. Reported is the rate of change in total points per month. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Agreement Between the Weights Obtained by Patients and Study Coordinator | Month 1, Month 12 | To confirm that participants can accurately measure their own weight, even as they become more disabled by ALS, the investigators will compare the participant-generated weight with the weight obtained by the study coordinator at the Month 1 and Month 12 visits. A simple description of the accuracy (percent agreement between the weights) will be used. |
| Enrollment Rate | Screening/baseline - Month 12 | Rate of enrollment in reaching the 50 participants required to fill the trial. |
| Change in H3 Histone Acetylation | Screening/baseline, Month 1 | Participants, ALS controls (not on Lunasin) and healthy controls (not on Lunasin) had blood drawn at baseline and 1 month time points. Histones were extracted from blood cells. Western blots were used to look at specific histone acetylation patterns that Lunasin had reportedly altered in cell cultures (H3K9K14ac2 and H4K5K8K12K16). Integrated density values for AcH3 protein bands were normalized for total H3. Percent H3 values for the 1 month time point were normalized to that of the baseline visit. Results were analyzed by one-way ANOVA. |
| Frequency of ALS Reversals | Screening/baseline - Month 12 | The percentage of enrolled participants experiencing an ALSFRS-R improvement of at least 4 points lasting at least 12 months. |
| ALSFRS-R Accuracy | Month 1 | To confirm that participants can accurately measure their own ALS Functional Rating Scale (Revised, ALSFRS-R), the investigators will compare the ALSFRS-R obtained by the coordinator with that obtained by the participants themselves at the Month 1 Visit. Correlational analysis between these 2 scores will be performed with Spearman's rho. |
| Retention Rate | Month 12 | Percentage of surviving participants who completed the month 12 visit. |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited from the clinic patient population and outside advertisements and postings. Recruitment began 3/28/2016 and ended 9/14/16 once 50 subjects had been enrolled. Study visits were conducted at the Duke ALS clinic and via phone contacts.
Pre-assignment details
An additional 10 subjects were consented specifically as controls for outcome measure 2 and not included in the treatment group (Lunasin regimen).
Participants by arm
| Arm | Count |
|---|---|
| Lunasin Regimen The Lunasin regimen consists of:
* LunaRich X Capsules (12 capsules per day)
* Reliv NOW - a mixture of 'vitamins, minerals and super-powered antioxidants' (3 scoops per day)
* Pro-Vantage - a mixture of 'soy protein, medium chain triglycerides, creatine, CoQ10 and supercharged amino acids' (2 scoops per day)
It will be suggested that patients open the LunaRich X capsules and mix the contents of these as well as the other 2 ingredients in water to make a shake. If patients do not tolerate advancing to the next dosage, they will be asked to drop back to the highest dosage they could tolerate.
Lunasin Regimen: LunaRich X Capsules, Reliv Now, ProVantage | 50 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 5 | 0 |
| Overall Study | Lost to Follow-up | 2 | 0 |
| Overall Study | Physician Decision | 2 | 0 |
| Overall Study | Withdrawal by Subject | 4 | 0 |
Baseline characteristics
| Characteristic | Lunasin Regimen |
|---|---|
| Age, Continuous | 60 years STANDARD_DEVIATION 7.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 49 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 47 Participants |
| Region of Enrollment United States | 50 Participants |
| Sex: Female, Male Female | 21 Participants |
| Sex: Female, Male Male | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 5 / 50 |
| other Total, other adverse events | 45 / 50 |
| serious Total, serious adverse events | 13 / 50 |
Outcome results
Primary
Change in Revised ALS Functional Rating Scale (ALSFRS-R)
ALSFRS-R is a quickly administered (five minute) ordinal rating scale used to determine patient's assessment of their capability and independence in 13 functional activities. All 13 activities are relevant in ALS. Each task is rated on a five-point scale from 0 = can't do, to 4 = normal ability, with a total score of 52 points. Reported is the rate of change in total points per month.
Time frame: Screening/baseline - 12 months
Population: 1 participant deleted PLM account; 2 others did not enter ALSFRS-R data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lunasin Regimen | Change in Revised ALS Functional Rating Scale (ALSFRS-R) | 0.44 points per month | Standard Deviation 1.6 |
Comparison: Matched historical controls will be identified from the PatientsLikeMe database.p-value: 0.99Kolmogorov-Smirnov Test
Secondary
ALSFRS-R Accuracy
To confirm that participants can accurately measure their own ALS Functional Rating Scale (Revised, ALSFRS-R), the investigators will compare the ALSFRS-R obtained by the coordinator with that obtained by the participants themselves at the Month 1 Visit. Correlational analysis between these 2 scores will be performed with Spearman's rho.
Time frame: Month 1
Population: 2 participants did not provide month 1 scores.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Lunasin Regimen | ALSFRS-R Accuracy | 99.39 percentage of accuracy |
p-value: <0.00001Lin's Concordance
Secondary
Change in H3 Histone Acetylation
Participants, ALS controls (not on Lunasin) and healthy controls (not on Lunasin) had blood drawn at baseline and 1 month time points. Histones were extracted from blood cells. Western blots were used to look at specific histone acetylation patterns that Lunasin had reportedly altered in cell cultures (H3K9K14ac2 and H4K5K8K12K16). Integrated density values for AcH3 protein bands were normalized for total H3. Percent H3 values for the 1 month time point were normalized to that of the baseline visit. Results were analyzed by one-way ANOVA.
Time frame: Screening/baseline, Month 1
Population: Lunasin regimen: 20 of 50 enrolled participants did not have sufficient sample. Five ALS control subjects (not on Lunasin) and five healthy control subjects (not on Lunasin) were also consented specifically for this analysis. One of the healthy controls did not have sufficient sample.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lunasin Regimen | Change in H3 Histone Acetylation | 0.993 percentage of baseline | Standard Deviation 0.53 |
| ALS Controls | Change in H3 Histone Acetylation | 1.252 percentage of baseline | Standard Deviation 0.74 |
| Healthy Controls | Change in H3 Histone Acetylation | 1.795 percentage of baseline | Standard Deviation 1.29 |
p-value: 0.0748ANOVA
Secondary
Enrollment Rate
Rate of enrollment in reaching the 50 participants required to fill the trial.
Time frame: Screening/baseline - Month 12
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lunasin Regimen | Enrollment Rate | 9.1 participants per month |
Secondary
Frequency of ALS Reversals
The percentage of enrolled participants experiencing an ALSFRS-R improvement of at least 4 points lasting at least 12 months.
Time frame: Screening/baseline - Month 12
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lunasin Regimen | Frequency of ALS Reversals | 0 percentage of participants |
Secondary
Percent Agreement Between the Weights Obtained by Patients and Study Coordinator
To confirm that participants can accurately measure their own weight, even as they become more disabled by ALS, the investigators will compare the participant-generated weight with the weight obtained by the study coordinator at the Month 1 and Month 12 visits. A simple description of the accuracy (percent agreement between the weights) will be used.
Time frame: Month 1, Month 12
Population: Participants with both self-obtained weight and weight obtained by the study coordinator available.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lunasin Regimen | Percent Agreement Between the Weights Obtained by Patients and Study Coordinator | Month 1 | 99.47 percentage of agreement |
| Lunasin Regimen | Percent Agreement Between the Weights Obtained by Patients and Study Coordinator | Month 12 | 99.05 percentage of agreement |
p-value: <0.00001Lin's Concordance
Secondary
Retention Rate
Percentage of surviving participants who completed the month 12 visit.
Time frame: Month 12
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lunasin Regimen | Retention Rate | 84 percentage of participants |