Amyotrophic Lateral Sclerosis
Conditions
Brief summary
This will be a 6-month, widely inclusive, virtual, single-center, open-label pilot trial utilizing a historical control group.
Detailed description
This will be a 6-month, widely inclusive, virtual, single-center, open-label pilot trial utilizing a historical control group. Following informed consent and screening, participants with ALS will take Theracurmin 1 capsule (90mg) twice daily for 6-months. Treatment with the Theracurmin and all study outcome measures and labs are being performed exclusively for research purposes. Collected data includes saliva and stool microbiome sampling, adverse events, concomitant medications, weight and height, Theracurmin treatment evaluations, and Thrive Questionnaires. Participants will be asked to register on the website Patientslikeme.
Interventions
DRUGTheracurmin HP
The intervention is based on the twice daily dosage of Theracurmin 90 mg capsules used in a trial of patients with mild cognitive impairment
Sponsors
Richard Bedlack, M.D., Ph.D.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This will be a 6-month, widely inclusive, largely remote/virtual, single-center, open-label pilot trial utilizing a historical control group.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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. * Patient is expected to survive for the duration of the trial. * Women must not be pregnant (will have evidence of a negative pregnancy test obtained by local physician within past 7 days or be post-menopausal) * 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 (those that are part of an active research study). * Prior side effects from curcumin or turmeric containing products * 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. * Life expectancy shorter than the duration of the trial. * Taking an antiplatelet agent or anticoagulant (due to the theoretically increased risk of bleeding from curcumin products).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in ALSFRS-R Slope | Starting at week 4 and then once every 30 days for 6 months | The ALSFRS-R (ALS Functional Rating Scale-Revised) will be determined at all video/telephone visits. ALSFRS-R is a quickly administered (five minute) ordinal rating scale (ratings 0-4) used to determine patients' assessments of their capability and independence in 12 functional activities. All 12 activities are relevant in ALS. Change in ALSFRS-R scores correlate with change in strength over time, and it is closely associated with quality of life measures and predicted survival. Each task is rated on a five-point scale from 0 = can't do, to 4 = normal ability. Individual item scores are summed to produce a reported score of between 0=worst and 48=best. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total Number of Adverse Events as Measured by Patient Reporting | up to 6 months | Adverse and serious adverse events will be recorded throughout the study. |
| Enrollment Rate | up to 6 months | The number of participants enrolled divided by the number of months it took to enroll them. |
| Retention as Measured by the Number of Participants Who Completed the 6 Month Study Visit | month 6 | The percentage of enrolled participants who completed the 6 month study visit. |
| Shannon Diversity Index of the Oral Microbiome | Baseline, month 1, month 6 | Comparing the changes in the saliva microbiome over time in patients with ALS on Theracurmin to the changes observed in untreated healthy controls. Data will be compared within subjects with ALS to assess possible changes over the length of the study and identify microbial correlates of disease progression. The Shannon diversity index takes into account the number of species living in a habitat (richness) and their relative abundance (evenness). The minimum value is 0, which indicates no diversity (only one species is found). There is no upper limit to the index; the maximum value occurs when all species have the same number of individuals. Baseline was compared to post-treatment samples from months 1 and 6 analyzed together. |
| Faith's Phylogenetic Diversity of the Oral Microbiome | Baseline, month 1, and month 6 | Comparing the changes in the saliva microbiome over time in patients with ALS on Theracurmin to the changes observed in untreated healthy controls. Data will be compared within subjects with ALS to assess possible changes over the length of the study and identify microbial correlates of disease progression. Phylogenetic diversity (PD) is a measure of biodiversity, based on phylogeny (the tree of life). PD is defined as equal to the sum of the lengths of all the branches on the tree that span the members of the set. The branch lengths on the tree count the relative number of new features arising along that part of the tree. Baseline was compared to post-treatment samples from months 1 and 6 analyzed together. |
| Number of Participants With ALS Reversal | Month 6 | Number of participants who have an ALSFRS-R (Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised) score that improves by 4 points or more over 6 months. The ALSFRS-R is used to determine patients' assessments of their capability and independence in 12 functional activities. All 12 activities are relevant in ALS. Change in ALSFRS-R scores correlate with change in strength over time, and it is closely associated with quality of life measures and predicted survival. Each task is rated on a five-point scale from 0 = can't do, to 4 = normal ability. Individual item scores are summed to produce a reported score of between 0=worst and 48=best. |
| Pielou's Evenness Index of the Oral Microbiome | Baseline, month 1, month 6 | Comparing the changes in the saliva microbiome over time in patients with ALS on Theracurmin to the changes observed in untreated healthy controls. Data will be compared within subjects with ALS to assess possible changes over the length of the study and identify microbial correlates of disease progression. Pielou's evenness is an index that measures diversity along with species richness. While species richness is the number of different species in a given area, evenness is the count of individuals of each species in an area. A calculated value of Pielou's evenness ranges from 0 (no evenness) to 1 (complete evenness). Baseline was compared to post-treatment samples from months 1 and 6 analyzed together. |
| Shannon Diversity Index of the Stool Microbiome | Baseline, month 1, month 6 | The microbiome of study participants will be analyzed in stool samples at enrollment, week 4 and month 6 visits. Changes will be compared in the stool microbiome over time in patients with ALS on Theracurmin to the changes observed in untreated healthy controls. The Shannon diversity index takes into account the number of species living in a habitat (richness) and their relative abundance (evenness). The minimum value is 0, which indicates no diversity (only one species is found). There is no upper limit to the index; the maximum value occurs when all species have the same number of individuals. Baseline was compared to post-treatment samples from months 1 and 6 analyzed together. |
| Faith's Phylogenetic Diversity of the Stool Microbiome | Baseline, month 1, month 6 | The microbiome of study participants will be analyzed in stool samples at enrollment, week 4 and month 6 visits. Changes will be compared in the stool microbiome over time in patients with ALS on Theracurmin to the changes observed in untreated healthy controls. Metagenomic analysis of deidentified selected fecal sample will be done on patients that positively respond to Theracurmin to achieve strain level identification of microbes positively and negatively associated with improved outcomes. Phylogenetic diversity (PD) is a measure of biodiversity, based on phylogeny (the tree of life). PD is defined as equal to the sum of the lengths of all the branches on the tree that span the members of the set. The branch lengths on the tree count the relative number of new features arising along that part of the tree. Baseline was compared to post-treatment samples from months 1 and 6 analyzed together. |
| Observed Features (Amplicon Sequence Variants, ASVs) of the Stool Microbiome | Baseline, month 1, month 6 | The microbiome of study participants will be analyzed in stool samples at enrollment, week 4 and month 6 visits. Changes will be compared in the stool microbiome over time in patients with ALS on Theracurmin to the changes observed in untreated healthy controls. An amplicon sequence variant (ASV) is any one of the inferred single DNA sequences recovered from a high-throughput analysis of marker genes. Baseline was compared to post-treatment samples from months 1 and 6 analyzed together. |
| Pielou's Evenness Index of the Stool Microbiome | Baseline, month 1, month 6 | The microbiome of study participants will be analyzed in stool samples at enrollment, week 4 and month 6 visits. Changes will be compared in the stool microbiome over time in patients with ALS on Theracurmin to the changes observed in untreated healthy controls. Pielou's evenness is an index that measures diversity along with species richness. While species richness is the number of different species in a given area, evenness is the count of individuals of each species in an area. A calculated value of Pielou's evenness ranges from 0 (no evenness) to 1 (complete evenness). Baseline was compared to post-treatment samples from months 1 and 6 analyzed together. |
| Observed Features (Amplicon Sequence Variants, ASV) of the Oral Microbiome | Baseline, month 1, month 6 | Comparing the changes in the saliva microbiome over time in patients with ALS on Theracurmin to the changes observed in untreated healthy controls. Data will be compared within subjects with ALS to assess possible changes over the length of the study and identify microbial correlates of disease progression. An amplicon sequence variant (ASV) is any one of the inferred single DNA sequences recovered from a high-throughput analysis of marker genes. Baseline was compared to post-treatment samples from months 1 and 6 analyzed together. |
Countries
United States
Participant flow
Recruitment details
Patients were recruited through the Duke ALS Clinic over a 16 month period.
Pre-assignment details
Patients with ALS who met inclusion criteria were enrolled into the Open Label Arm. The healthy control arm was for people without ALS who came from the same household as the patients.
Participants by arm
| Arm | Count |
|---|---|
| Open Label Arm The intervention is twice daily dosage of Theracurmin 90 mg capsules. This same dose was used in a successful trial of patients with mild cognitive impairment. Theracurmin HP capsules containing 90 mg curcumin each that will be taken as one capsule twice daily for 6 months. Each capsule contains 300 mg Theracurmin enhanced bioavailable water-dispersible turmeric rhizome complex providing 30% curcumin (90 mg). The content of Theracurmin HP has been independently certified by NSF International under NSF/ANSI 173.
Theracurmin HP: The intervention is based on the twice daily dosage of Theracurmin 90 mg capsules used in a trial of patients with mild cognitive impairment | 50 |
| Healthy Control Arm We will seek to enroll 50 healthy control participants. We will attempt to enroll one control subject from each enrolled primary participant's home, preferably a spouse or partner of similar age if possible. We plan to use this data to compare the microbiome of control participants to that of the ALS participants at baseline, week 4 and month 6. We will not conduct further follow-up or collect additional samples with the control subjects. | 0 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 0 |
| Overall Study | Death | 3 | 0 |
| Overall Study | Lack of Efficacy | 7 | 0 |
| Overall Study | Lost to Follow-up | 2 | 0 |
Baseline characteristics
| Characteristic | Open Label Arm | Total |
|---|---|---|
| Age, Continuous | 60.96 years STANDARD_DEVIATION 11.46 | 60.96 years STANDARD_DEVIATION 11.46 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 3 Participants |
| Race (NIH/OMB) White | 43 Participants | 43 Participants |
| Region of Enrollment United States | 50 Participants | 50 Participants |
| Sex: Female, Male Female | 19 Participants | 19 Participants |
| Sex: Female, Male Male | 31 Participants | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 50 | 0 / 0 |
| other Total, other adverse events | 23 / 50 | 0 / 0 |
| serious Total, serious adverse events | 1 / 50 | 0 / 0 |
Outcome results
Primary
Change in ALSFRS-R Slope
The ALSFRS-R (ALS Functional Rating Scale-Revised) will be determined at all video/telephone visits. ALSFRS-R is a quickly administered (five minute) ordinal rating scale (ratings 0-4) used to determine patients' assessments of their capability and independence in 12 functional activities. All 12 activities are relevant in ALS. Change in ALSFRS-R scores correlate with change in strength over time, and it is closely associated with quality of life measures and predicted survival. Each task is rated on a five-point scale from 0 = can't do, to 4 = normal ability. Individual item scores are summed to produce a reported score of between 0=worst and 48=best.
Time frame: Starting at week 4 and then once every 30 days for 6 months
Population: Participants with ALSFRS-R scores available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Open Label Arm | Change in ALSFRS-R Slope | 0.229 ALSFRS-R points per week | Standard Deviation 0.274 |
| Healthy Control Arm | Change in ALSFRS-R Slope | 0.224 ALSFRS-R points per week | Standard Deviation 0.194 |
Comparison: We compared he ALSFRS-R slope (not the actual score) of the patients in our open label treatment versus the historical controls.p-value: 0.984t-test, 2 sided
Secondary
Enrollment Rate
The number of participants enrolled divided by the number of months it took to enroll them.
Time frame: up to 6 months
Population: Data not collected on the healthy control arm.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Open Label Arm | Enrollment Rate | 3.1 participants per month |
Secondary
Faith's Phylogenetic Diversity of the Oral Microbiome
Comparing the changes in the saliva microbiome over time in patients with ALS on Theracurmin to the changes observed in untreated healthy controls. Data will be compared within subjects with ALS to assess possible changes over the length of the study and identify microbial correlates of disease progression. Phylogenetic diversity (PD) is a measure of biodiversity, based on phylogeny (the tree of life). PD is defined as equal to the sum of the lengths of all the branches on the tree that span the members of the set. The branch lengths on the tree count the relative number of new features arising along that part of the tree. Baseline was compared to post-treatment samples from months 1 and 6 analyzed together.
Time frame: Baseline, month 1, and month 6
Population: Participants with samples collected. Post-treatment samples from months 1 and 6 were analyzed together.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Open Label Arm | Faith's Phylogenetic Diversity of the Oral Microbiome | Baseline | 13.5 units of PD |
| Open Label Arm | Faith's Phylogenetic Diversity of the Oral Microbiome | Post-treatment (months 1 and 6 combined) | 13.2 units of PD |
| Healthy Control Arm | Faith's Phylogenetic Diversity of the Oral Microbiome | Baseline | 12.8 units of PD |
| Healthy Control Arm | Faith's Phylogenetic Diversity of the Oral Microbiome | Post-treatment (months 1 and 6 combined) | 12.7 units of PD |
Comparison: Open Label Arm participant samples from baseline, month 1, and month 6.p-value: >0.5Kruskal-Wallis
Secondary
Faith's Phylogenetic Diversity of the Stool Microbiome
The microbiome of study participants will be analyzed in stool samples at enrollment, week 4 and month 6 visits. Changes will be compared in the stool microbiome over time in patients with ALS on Theracurmin to the changes observed in untreated healthy controls. Metagenomic analysis of deidentified selected fecal sample will be done on patients that positively respond to Theracurmin to achieve strain level identification of microbes positively and negatively associated with improved outcomes. Phylogenetic diversity (PD) is a measure of biodiversity, based on phylogeny (the tree of life). PD is defined as equal to the sum of the lengths of all the branches on the tree that span the members of the set. The branch lengths on the tree count the relative number of new features arising along that part of the tree. Baseline was compared to post-treatment samples from months 1 and 6 analyzed together.
Time frame: Baseline, month 1, month 6
Population: Participants with samples collected. Post-treatment samples from months 1 and 6 were analyzed together.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Open Label Arm | Faith's Phylogenetic Diversity of the Stool Microbiome | Baseline | 10.8 units of PD |
| Open Label Arm | Faith's Phylogenetic Diversity of the Stool Microbiome | Post-treatment (months 1 and 6 combined) | 10.8 units of PD |
| Healthy Control Arm | Faith's Phylogenetic Diversity of the Stool Microbiome | Baseline | 10.4 units of PD |
| Healthy Control Arm | Faith's Phylogenetic Diversity of the Stool Microbiome | Post-treatment (months 1 and 6 combined) | 10.6 units of PD |
Comparison: Open Label Arm participant samples from baseline, month 1, and month 6.p-value: >0.05Kruskal-Wallis
Secondary
Number of Participants With ALS Reversal
Number of participants who have an ALSFRS-R (Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised) score that improves by 4 points or more over 6 months. The ALSFRS-R is used to determine patients' assessments of their capability and independence in 12 functional activities. All 12 activities are relevant in ALS. Change in ALSFRS-R scores correlate with change in strength over time, and it is closely associated with quality of life measures and predicted survival. Each task is rated on a five-point scale from 0 = can't do, to 4 = normal ability. Individual item scores are summed to produce a reported score of between 0=worst and 48=best.
Time frame: Month 6
Population: Two open label arm participants withdrew consent after enrollment. Data not collected on the healthy control arm.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Open Label Arm | Number of Participants With ALS Reversal | 0 Participants |
Secondary
Observed Features (Amplicon Sequence Variants, ASV) of the Oral Microbiome
Comparing the changes in the saliva microbiome over time in patients with ALS on Theracurmin to the changes observed in untreated healthy controls. Data will be compared within subjects with ALS to assess possible changes over the length of the study and identify microbial correlates of disease progression. An amplicon sequence variant (ASV) is any one of the inferred single DNA sequences recovered from a high-throughput analysis of marker genes. Baseline was compared to post-treatment samples from months 1 and 6 analyzed together.
Time frame: Baseline, month 1, month 6
Population: Participants with samples collected. Post-treatment samples from months 1 and 6 were analyzed together.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Open Label Arm | Observed Features (Amplicon Sequence Variants, ASV) of the Oral Microbiome | Baseline | 121.4 ASVs |
| Open Label Arm | Observed Features (Amplicon Sequence Variants, ASV) of the Oral Microbiome | Post-treatment (months 1 and 6 combined) | 115.1 ASVs |
| Healthy Control Arm | Observed Features (Amplicon Sequence Variants, ASV) of the Oral Microbiome | Baseline | 114.4 ASVs |
| Healthy Control Arm | Observed Features (Amplicon Sequence Variants, ASV) of the Oral Microbiome | Post-treatment (months 1 and 6 combined) | 110.6 ASVs |
Comparison: Open Label Arm participant samples from baseline, month 1, and month 6.p-value: >0.05Kruskal-Wallis
Secondary
Observed Features (Amplicon Sequence Variants, ASVs) of the Stool Microbiome
The microbiome of study participants will be analyzed in stool samples at enrollment, week 4 and month 6 visits. Changes will be compared in the stool microbiome over time in patients with ALS on Theracurmin to the changes observed in untreated healthy controls. An amplicon sequence variant (ASV) is any one of the inferred single DNA sequences recovered from a high-throughput analysis of marker genes. Baseline was compared to post-treatment samples from months 1 and 6 analyzed together.
Time frame: Baseline, month 1, month 6
Population: Participants with samples collected. Post-treatment samples from months 1 and 6 were analyzed together.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Open Label Arm | Observed Features (Amplicon Sequence Variants, ASVs) of the Stool Microbiome | Baseline | 146.1 ASVs |
| Open Label Arm | Observed Features (Amplicon Sequence Variants, ASVs) of the Stool Microbiome | Post-treatment (months 1 and 6 combined) | 148.2 ASVs |
| Healthy Control Arm | Observed Features (Amplicon Sequence Variants, ASVs) of the Stool Microbiome | Baseline | 145.7 ASVs |
| Healthy Control Arm | Observed Features (Amplicon Sequence Variants, ASVs) of the Stool Microbiome | Post-treatment (months 1 and 6 combined) | 146.8 ASVs |
Comparison: Open Label Arm participant samples from baseline, month 1, and month 6.p-value: >0.05Kruskal-Wallis
Secondary
Pielou's Evenness Index of the Oral Microbiome
Comparing the changes in the saliva microbiome over time in patients with ALS on Theracurmin to the changes observed in untreated healthy controls. Data will be compared within subjects with ALS to assess possible changes over the length of the study and identify microbial correlates of disease progression. Pielou's evenness is an index that measures diversity along with species richness. While species richness is the number of different species in a given area, evenness is the count of individuals of each species in an area. A calculated value of Pielou's evenness ranges from 0 (no evenness) to 1 (complete evenness). Baseline was compared to post-treatment samples from months 1 and 6 analyzed together.
Time frame: Baseline, month 1, month 6
Population: Participants with samples collected. Post-treatment samples from months 1 and 6 were analyzed together.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Open Label Arm | Pielou's Evenness Index of the Oral Microbiome | Baseline | 0.69 Pielou's evenness index |
| Open Label Arm | Pielou's Evenness Index of the Oral Microbiome | Post-treatment (months 1 and 6 combined) | 0.69 Pielou's evenness index |
| Healthy Control Arm | Pielou's Evenness Index of the Oral Microbiome | Baseline | 0.69 Pielou's evenness index |
| Healthy Control Arm | Pielou's Evenness Index of the Oral Microbiome | Post-treatment (months 1 and 6 combined) | 0.70 Pielou's evenness index |
Comparison: Open Label Arm participant samples from baseline, month 1, and month 6.p-value: >0.05Kruskal-Wallis
Secondary
Pielou's Evenness Index of the Stool Microbiome
The microbiome of study participants will be analyzed in stool samples at enrollment, week 4 and month 6 visits. Changes will be compared in the stool microbiome over time in patients with ALS on Theracurmin to the changes observed in untreated healthy controls. Pielou's evenness is an index that measures diversity along with species richness. While species richness is the number of different species in a given area, evenness is the count of individuals of each species in an area. A calculated value of Pielou's evenness ranges from 0 (no evenness) to 1 (complete evenness). Baseline was compared to post-treatment samples from months 1 and 6 analyzed together.
Time frame: Baseline, month 1, month 6
Population: Participants with samples collected. Post-treatment samples from months 1 and 6 were analyzed together.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Open Label Arm | Pielou's Evenness Index of the Stool Microbiome | Baseline | 0.72 Pielou's evenness index |
| Open Label Arm | Pielou's Evenness Index of the Stool Microbiome | Post-treatment (months 1 and 6 combined) | 0.73 Pielou's evenness index |
| Healthy Control Arm | Pielou's Evenness Index of the Stool Microbiome | Baseline | 0.74 Pielou's evenness index |
| Healthy Control Arm | Pielou's Evenness Index of the Stool Microbiome | Post-treatment (months 1 and 6 combined) | 0.73 Pielou's evenness index |
Comparison: Open Label Arm participant samples from baseline, month 1, and month 6.p-value: >0.05Kruskal-Wallis
Secondary
Retention as Measured by the Number of Participants Who Completed the 6 Month Study Visit
The percentage of enrolled participants who completed the 6 month study visit.
Time frame: month 6
Population: Data not collected on the healthy control arm.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Open Label Arm | Retention as Measured by the Number of Participants Who Completed the 6 Month Study Visit | 35 Participants |
Secondary
Shannon Diversity Index of the Oral Microbiome
Comparing the changes in the saliva microbiome over time in patients with ALS on Theracurmin to the changes observed in untreated healthy controls. Data will be compared within subjects with ALS to assess possible changes over the length of the study and identify microbial correlates of disease progression. The Shannon diversity index takes into account the number of species living in a habitat (richness) and their relative abundance (evenness). The minimum value is 0, which indicates no diversity (only one species is found). There is no upper limit to the index; the maximum value occurs when all species have the same number of individuals. Baseline was compared to post-treatment samples from months 1 and 6 analyzed together.
Time frame: Baseline, month 1, month 6
Population: Participants with samples collected. Post-treatment samples from months 1 and 6 were analyzed together.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Open Label Arm | Shannon Diversity Index of the Oral Microbiome | Baseline | 4.7 Shannon diversity index |
| Open Label Arm | Shannon Diversity Index of the Oral Microbiome | Post-treatment (months 1 and 6 combined) | 4.7 Shannon diversity index |
| Healthy Control Arm | Shannon Diversity Index of the Oral Microbiome | Baseline | 4.7 Shannon diversity index |
| Healthy Control Arm | Shannon Diversity Index of the Oral Microbiome | Post-treatment (months 1 and 6 combined) | 4.7 Shannon diversity index |
Comparison: Open Label Arm participant samples from baseline, month 1, and month 6.p-value: >0.05Kruskal-Wallis
Secondary
Shannon Diversity Index of the Stool Microbiome
The microbiome of study participants will be analyzed in stool samples at enrollment, week 4 and month 6 visits. Changes will be compared in the stool microbiome over time in patients with ALS on Theracurmin to the changes observed in untreated healthy controls. The Shannon diversity index takes into account the number of species living in a habitat (richness) and their relative abundance (evenness). The minimum value is 0, which indicates no diversity (only one species is found). There is no upper limit to the index; the maximum value occurs when all species have the same number of individuals. Baseline was compared to post-treatment samples from months 1 and 6 analyzed together.
Time frame: Baseline, month 1, month 6
Population: Participants with samples collected. Post-treatment samples from months 1 and 6 were analyzed together.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Open Label Arm | Shannon Diversity Index of the Stool Microbiome | Baseline | 5.1 Shannon diversity index |
| Open Label Arm | Shannon Diversity Index of the Stool Microbiome | Post-treatment (months 1 and 6 combined) | 5.2 Shannon diversity index |
| Healthy Control Arm | Shannon Diversity Index of the Stool Microbiome | Baseline | 5.3 Shannon diversity index |
| Healthy Control Arm | Shannon Diversity Index of the Stool Microbiome | Post-treatment (months 1 and 6 combined) | 5.2 Shannon diversity index |
Comparison: Open Label Arm participant samples from baseline, month 1, and month 6.p-value: >0.05Kruskal-Wallis
Secondary
Total Number of Adverse Events as Measured by Patient Reporting
Adverse and serious adverse events will be recorded throughout the study.
Time frame: up to 6 months
Population: Two open label arm participants withdrew consent after enrollment. Data not collected on the healthy control arm.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Open Label Arm | Total Number of Adverse Events as Measured by Patient Reporting | 25 adverse events |