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

Study Overview
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Brief Summary
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This will be a 6-month, widely inclusive, virtual, single-center, open-label pilot trial utilizing a historical control group.

Detailed Description
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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.

Official Title
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An Open-label, Single-center, 6-month Trial of Theracurmin for Patients With Amyotrophic Lateral Sclerosis (ALS)

Conditions
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Amyotrophic Lateral Sclerosis

Intervention / Treatment
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* Drug: Theracurmin HP


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This will be a 6-month, widely inclusive, largely remote/virtual, single-center, open-label pilot trial utilizing a historical control group.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Open Label Arm<br>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. | Drug: Theracurmin HP<br>* The intervention is based on the twice daily dosage of Theracurmin 90 mg capsules used in a trial of patients with mild cognitive impairment<br>|
| No Intervention: Healthy Control Arm<br>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. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Starting at week 4 and then once every 30 days for 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Month 6 | 
| Total Number of Adverse Events as Measured by Patient Reporting | Adverse and serious adverse events will be recorded throughout the study. | up to 6 months | 
| Enrollment Rate | The number of participants enrolled divided by the number of months it took to enroll them. | up to 6 months | 
| 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. | month 6 | 
| 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. | Baseline, month 1, month 6 | 
| 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. | Baseline, month 1, and month 6 | 
| 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. | Baseline, month 1, month 6 | 
| 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. | Baseline, month 1, month 6 | 
| 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. | Baseline, month 1, month 6 | 
| 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. | Baseline, month 1, month 6 | 
| 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. | Baseline, month 1, month 6 | 
| 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. | Baseline, month 1, month 6 |