Trial Outcomes & Findings for Trial of Theracurmin for Patients With Amyotrophic Lateral Sclerosis (ALS) (NCT NCT04499963)

NCT ID: NCT04499963

Last Updated: 2023-09-28

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 100 participants
• Primary outcome timeframe: Starting at week 4 and then once every 30 days for 6 months
• Results posted on: 2023-09-28

Participant Flow

Patients were recruited through the Duke ALS Clinic over a 16 month period.

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.

Participant milestones

Measure	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	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.
Overall Study STARTED	50	50
Overall Study COMPLETED	35	50
Overall Study NOT COMPLETED	15	0

Reasons for withdrawal

Measure	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	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.
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

Trial of Theracurmin for Patients With Amyotrophic Lateral Sclerosis (ALS)

Baseline characteristics by cohort

Measure	Open Label Arm n=50 Participants 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	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.	Total n=50 Participants Total of all reporting groups
Age, Continuous	60.96 years STANDARD_DEVIATION 11.46 • n=5 Participants	—	60.96 years STANDARD_DEVIATION 11.46 • n=5 Participants
Sex: Female, Male Female	19 Participants n=5 Participants	—	19 Participants n=5 Participants
Sex: Female, Male Male	31 Participants n=5 Participants	—	31 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	—	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	—	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	—	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants	—	3 Participants n=5 Participants
Race (NIH/OMB) White	43 Participants n=5 Participants	—	43 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	—	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	—	3 Participants n=5 Participants
Region of Enrollment United States	50 Participants n=5 Participants	—	50 Participants n=5 Participants

PRIMARY outcome

Timeframe: Starting at week 4 and then once every 30 days for 6 months

Population: Participants with ALSFRS-R scores available.

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.

Outcome measures

Measure	Open Label Arm n=48 Participants 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	Healthy Control Arm n=44 Participants 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.
Change in ALSFRS-R Slope	0.229 ALSFRS-R points per week Standard Deviation 0.274	0.224 ALSFRS-R points per week Standard Deviation 0.194

SECONDARY outcome

Timeframe: Month 6

Population: Two open label arm participants withdrew consent after enrollment. Data not collected on the healthy control arm.

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.

Outcome measures

Measure	Open Label Arm n=48 Participants 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	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.
Number of Participants With ALS Reversal	0 Participants	—

SECONDARY outcome

Timeframe: up to 6 months

Population: Two open label arm participants withdrew consent after enrollment. Data not collected on the healthy control arm.

Adverse and serious adverse events will be recorded throughout the study.

Outcome measures

Measure	Open Label Arm n=48 Participants 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	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.
Total Number of Adverse Events as Measured by Patient Reporting	25 adverse events	—

SECONDARY outcome

Timeframe: up to 6 months

Population: Data not collected on the healthy control arm.

The number of participants enrolled divided by the number of months it took to enroll them.

Outcome measures

Measure	Open Label Arm n=50 Participants 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	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.
Enrollment Rate	3.1 participants per month	—

SECONDARY outcome

Timeframe: month 6

Population: Data not collected on the healthy control arm.

The percentage of enrolled participants who completed the 6 month study visit.

Outcome measures

Measure	Open Label Arm n=50 Participants 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	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.
Retention as Measured by the Number of Participants Who Completed the 6 Month Study Visit	35 Participants	—

SECONDARY outcome

Timeframe: Baseline, month 1, month 6

Population: Participants with samples collected. Post-treatment samples from months 1 and 6 were analyzed together.

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.

Outcome measures

Measure	Open Label Arm n=117 samples 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	Healthy Control Arm n=107 samples 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.
Shannon Diversity Index of the Oral Microbiome Baseline	4.7 Shannon diversity index Interval 1.5 to 6.2	4.7 Shannon diversity index Interval 3.3 to 6.1
Shannon Diversity Index of the Oral Microbiome Post-treatment (months 1 and 6 combined)	4.7 Shannon diversity index Interval 2.0 to 6.1	4.7 Shannon diversity index Interval 2.8 to 6.5

SECONDARY outcome

Timeframe: Baseline, month 1, and month 6

Population: Participants with samples collected. Post-treatment samples from months 1 and 6 were analyzed together.

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.

Outcome measures

Measure	Open Label Arm n=117 samples 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	Healthy Control Arm n=107 samples 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.
Faith's Phylogenetic Diversity of the Oral Microbiome Baseline	13.5 units of PD Interval 7.6 to 17.7	12.8 units of PD Interval 8.6 to 17.3
Faith's Phylogenetic Diversity of the Oral Microbiome Post-treatment (months 1 and 6 combined)	13.2 units of PD Interval 8.3 to 19.3	12.7 units of PD Interval 8.3 to 18.4

SECONDARY outcome

Timeframe: Baseline, month 1, month 6

Population: Participants with samples collected. Post-treatment samples from months 1 and 6 were analyzed together.

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.

Outcome measures

Measure	Open Label Arm n=117 samples 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	Healthy Control Arm n=107 samples 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.
Observed Features (Amplicon Sequence Variants, ASV) of the Oral Microbiome Baseline	121.4 ASVs Interval 33.0 to 227.0	114.4 ASVs Interval 43.0 to 226.0
Observed Features (Amplicon Sequence Variants, ASV) of the Oral Microbiome Post-treatment (months 1 and 6 combined)	115.1 ASVs Interval 40.0 to 209.0	110.6 ASVs Interval 35.0 to 225.0

SECONDARY outcome

Timeframe: Baseline, month 1, month 6

Population: Participants with samples collected. Post-treatment samples from months 1 and 6 were analyzed together.

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.

Outcome measures

Measure	Open Label Arm n=117 samples 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	Healthy Control Arm n=107 samples 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.
Pielou's Evenness Index of the Oral Microbiome Baseline	0.69 Pielou's evenness index Interval 0.25 to 0.83	0.69 Pielou's evenness index Interval 0.56 to 0.8
Pielou's Evenness Index of the Oral Microbiome Post-treatment (months 1 and 6 combined)	0.69 Pielou's evenness index Interval 0.37 to 0.84	0.70 Pielou's evenness index Interval 0.45 to 0.83

SECONDARY outcome

Timeframe: Baseline, month 1, month 6

Population: Participants with samples collected. Post-treatment samples from months 1 and 6 were analyzed together.

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.

Outcome measures

Measure	Open Label Arm n=113 samples 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	Healthy Control Arm n=111 samples 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.
Shannon Diversity Index of the Stool Microbiome Baseline	5.1 Shannon diversity index Interval 3.5 to 6.2	5.3 Shannon diversity index Interval 2.9 to 6.8
Shannon Diversity Index of the Stool Microbiome Post-treatment (months 1 and 6 combined)	5.2 Shannon diversity index Interval 3.8 to 6.3	5.2 Shannon diversity index Interval 3.7 to 6.7

SECONDARY outcome

Timeframe: Baseline, month 1, month 6

Population: Participants with samples collected. Post-treatment samples from months 1 and 6 were analyzed together.

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.

Outcome measures

Measure	Open Label Arm n=113 samples 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	Healthy Control Arm n=111 samples 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.
Faith's Phylogenetic Diversity of the Stool Microbiome Baseline	10.8 units of PD Interval 5.2 to 19.5	10.4 units of PD Interval 4.8 to 17.9
Faith's Phylogenetic Diversity of the Stool Microbiome Post-treatment (months 1 and 6 combined)	10.8 units of PD Interval 4.7 to 18.1	10.6 units of PD Interval 5.1 to 18.6

SECONDARY outcome

Timeframe: Baseline, month 1, month 6

Population: Participants with samples collected. Post-treatment samples from months 1 and 6 were analyzed together.

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.

Outcome measures

Measure	Open Label Arm n=116 samples 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	Healthy Control Arm n=111 samples 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.
Observed Features (Amplicon Sequence Variants, ASVs) of the Stool Microbiome Baseline	146.1 ASVs Interval 50.0 to 268.0	145.7 ASVs Interval 62.0 to 265.0
Observed Features (Amplicon Sequence Variants, ASVs) of the Stool Microbiome Post-treatment (months 1 and 6 combined)	148.2 ASVs Interval 61.0 to 278.0	146.8 ASVs Interval 61.0 to 272.0

SECONDARY outcome

Timeframe: Baseline, month 1, month 6

Population: Participants with samples collected. Post-treatment samples from months 1 and 6 were analyzed together.

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.

Outcome measures

Measure	Open Label Arm n=116 samples 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	Healthy Control Arm n=111 samples 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.
Pielou's Evenness Index of the Stool Microbiome Baseline	0.72 Pielou's evenness index Interval 0.55 to 0.8	0.74 Pielou's evenness index Interval 0.47 to 0.84
Pielou's Evenness Index of the Stool Microbiome Post-treatment (months 1 and 6 combined)	0.73 Pielou's evenness index Interval 0.57 to 0.82	0.73 Pielou's evenness index Interval 0.56 to 0.83

Adverse Events

Open Label Arm

Serious events: 1 serious events

Other events: 23 other events

Deaths: 1 deaths

Healthy Control Arm

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	Open Label Arm n=50 participants at risk 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	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.
Respiratory, thoracic and mediastinal disorders Pulmonary embolus	2.0% 1/50 • Up to 6 months Adverse Events data not collected on the healthy control arm.	— 0/0 • Up to 6 months Adverse Events data not collected on the healthy control arm.

Other adverse events

Measure	Open Label Arm n=50 participants at risk 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	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.
Gastrointestinal disorders Diarrhea, loose stools	22.0% 11/50 • Up to 6 months Adverse Events data not collected on the healthy control arm.	— 0/0 • Up to 6 months Adverse Events data not collected on the healthy control arm.
General disorders Hot flashes	6.0% 3/50 • Up to 6 months Adverse Events data not collected on the healthy control arm.	— 0/0 • Up to 6 months Adverse Events data not collected on the healthy control arm.
Infections and infestations COVID Infection	6.0% 3/50 • Up to 6 months Adverse Events data not collected on the healthy control arm.	— 0/0 • Up to 6 months Adverse Events data not collected on the healthy control arm.
Skin and subcutaneous tissue disorders Itching	4.0% 2/50 • Up to 6 months Adverse Events data not collected on the healthy control arm.	— 0/0 • Up to 6 months Adverse Events data not collected on the healthy control arm.
General disorders Increased weakness	4.0% 2/50 • Up to 6 months Adverse Events data not collected on the healthy control arm.	— 0/0 • Up to 6 months Adverse Events data not collected on the healthy control arm.
General disorders Malaise	2.0% 1/50 • Up to 6 months Adverse Events data not collected on the healthy control arm.	— 0/0 • Up to 6 months Adverse Events data not collected on the healthy control arm.
Skin and subcutaneous tissue disorders Rash	2.0% 1/50 • Up to 6 months Adverse Events data not collected on the healthy control arm.	— 0/0 • Up to 6 months Adverse Events data not collected on the healthy control arm.
Psychiatric disorders Anxiety	2.0% 1/50 • Up to 6 months Adverse Events data not collected on the healthy control arm.	— 0/0 • Up to 6 months Adverse Events data not collected on the healthy control arm.
General disorders Flu-like symptoms	2.0% 1/50 • Up to 6 months Adverse Events data not collected on the healthy control arm.	— 0/0 • Up to 6 months Adverse Events data not collected on the healthy control arm.
Gastrointestinal disorders Constipation	2.0% 1/50 • Up to 6 months Adverse Events data not collected on the healthy control arm.	— 0/0 • Up to 6 months Adverse Events data not collected on the healthy control arm.
General disorders Abdominal pain	2.0% 1/50 • Up to 6 months Adverse Events data not collected on the healthy control arm.	— 0/0 • Up to 6 months Adverse Events data not collected on the healthy control arm.
General disorders Headache	2.0% 1/50 • Up to 6 months Adverse Events data not collected on the healthy control arm.	— 0/0 • Up to 6 months Adverse Events data not collected on the healthy control arm.
General disorders Cramps	2.0% 1/50 • Up to 6 months Adverse Events data not collected on the healthy control arm.	— 0/0 • Up to 6 months Adverse Events data not collected on the healthy control arm.

Additional Information

Richard Bedlack, MD, PhD

Duke University

Phone: 919-668-2839

Email: richard.bedlack@duke.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place