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

• ClinicalTrials.gov Identifier: NCT04499963
• Recruitment Status: Completed
• First Posted: August 5, 2020
• Last Update Posted: September 27, 2022
• Sponsor: Richard Bedlack, M.D., Ph.D.
• Information provided by (Responsible Party): Richard Bedlack, M.D., Ph.D., Duke University

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Amyotrophic Lateral Sclerosis	Drug: Theracurmin HP	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 68 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• 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.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label, Single-center, 6-month Trial of Theracurmin for Patients With Amyotrophic Lateral Sclerosis (ALS)
• Actual Study Start Date: August 28, 2020
• Actual Primary Completion Date: August 30, 2022
• Actual Study Completion Date: August 30, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: 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.	Drug: 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
No Intervention: 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.

Outcome Measures

Primary Outcome Measures :

1. Change in ALSFRS-R score [ Time Frame: 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 Outcome Measures :

1. ALS Reversals [ Time Frame: month 6 ]
   To look for an increase in the frequency of ALS reversals, we will count the number of participants who have an ALSFRS-R score that improves by 4 points or more over 6 months. The observed frequency of spontaneous ALS reversals defined in this way is 2-5% (30). We will look for an increase in this frequency to at least 10% (1 in 10).
2. Saliva Microbiome Sequencing change [ Time Frame: Enrollment, week 4 and month 6 visits ]
   The microbiome of study participants will be analyzed in saliva samples at enrollment, week 4 and month 6 visits. We will compare 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.
3. Number of adverse events as measured by patient reporting [ Time Frame: Study duration, up to 6 months ]
   Adverse and serious adverse events will be recorded throughout the study. The PI will determine whether these are related to treatment. Patients will also measure and record their side effects at Month 0-6 Internet Visits on their PLM profile.
4. Enrollment Rate [ Time Frame: one month ]
   Enrollment rate will be calculated as the number of participants enrolled per month.
5. Retention [ Time Frame: month 6 ]
   Retention will be assessed by looking at the dropout rate at 6 months (the percentage of surviving enrolled patients who complete the Month 6 Visit).
6. Stool Microbiome Sequencing change [ Time Frame: Enrollment, week 4 and month 6 visits ]
   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. The selected anaerobes that have been linked to ALS severity will be cultured for further genetic sand phenotypic characterization.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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).

Contacts and Locations

Locations

United States, North Carolina

Duke University Medical Center

Durham, North Carolina, United States, 27705

Sponsors and Collaborators

Richard Bedlack, M.D., Ph.D.

Investigators

• Principal Investigator: Richard Bedlack, MD, PhD; Duke University

More Information

• Responsible Party: Richard Bedlack, M.D., Ph.D., Professor of Neurology, Duke University
• ClinicalTrials.gov Identifier: NCT04499963
• Other Study ID Numbers: pro00103700
• First Posted: August 5, 2020
• Last Update Posted: September 27, 2022
• Last Verified: September 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Sclerosis; Pathologic Processes; Neurodegenerative Diseases; Nervous System Diseases; Neuromuscular Diseases; Spinal Cord Diseases; Central Nervous System Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Metabolic Diseases