ROAR-DIGAP: A Widely Inclusive, Largely Virtual Pilot Trial Utilizing DIGAP (Deep Integrated Genomics Analysis Platform) To Personalize Treatments

NCT06429059 | Completed Phase 2 FDA Drug

• 1 other identifier: Pro00114385
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 2

Brief Summary

GenieUs developed an analysis platform that will be tested to separate study participants with ALS into four categories based on blood work. These general categories are neuroinflammation, oxidative stress, impaired autophagy \& axonal transport, and mitochondrial dysfunction. Once a disease category is established, participants in this study will receive one of four individualized supplements for 6 months and we will determine whether these are slowing ALS progression: Astaxanthin will be given for the category of neuroinflammation, Protandim for oxidative stress, Melatonin for impaired autophagy and MitoQ for mitochondrial dysfunction. During the first 3 months, participants will have routine monitoring and in months 3 through 9 they will receive the assigned supplement.

Conditions

Amyotrophic Lateral Sclerosis ALS

Outcome Measures

Primary Outcomes (1)

• ALS Functional Rating Scale, Revised (ALSFRS-R)

  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 to people living with ALS.The ALSFRS-R declines linearly with time over a wide range during the course of ALS and it has been validated for telephone use.

  baseline and at each of the subsequent 9 telephone or in person visits (approximately 9 months)

Secondary Outcomes (8)

• Neurofilament Light Chain levels

  baseline, month 3, month 5 (2 months into treatment) and month 9 (6 months into treatment)

• Neuroinflammation measured by C-reactive protein (CRP)

  baseline, 3 months, 5 months and 9 months

• Neuroinflammation measured by monocyte chemoattractant protein-1 (MCP-1)

  baseline, 3 months, 5 months and 9 months

• Neuroinflammation measured by chitotriosidase (CHIT1)

  baseline, 3 months, 5 months and 9 months

• Oxidative stress measured by total antioxidant capacity (TAC)

  baseline, 3 months, 5 months and 9 months

Study Arms (4)

Neuroinflammation

EXPERIMENTAL

Study participants in this category are expected to have inflammation in their brains and spinal cords.

Drug: Astaxanthin

Oxidative Stress

EXPERIMENTAL

Study participants in this category are expected to have too many damaging "free radical" chemicals in their brains and spinal cords.

Drug: Protandim

Impaired Autophagy and Axonal Transport

EXPERIMENTAL

Study participants in this category are expected to have motor neurons that have trouble transporting materials up and down their length, and/or trouble with the turnover of damaged proteins and intracellular structures.

Drug: Melatonin

Mitochondrial Dysfunction

EXPERIMENTAL

Study participants in this category are expected to have motor neurons that are unable to produce normal amounts of energy.

Drug: MitoQ

Interventions

Astaxanthin DRUG

Astaxanthin is a red-orange natural pigment belonging to a group of carotenoids called xanthophylls. In nature, astaxanthin is synthesized by microalgae and phytoplankton and biomagnifies in higher marine animals through the food chain. Natural astaxanthin is available as capsules, soft gels, tablets, powders, biomass, creams, energy drinks, oils and extracts and often contains other carotenoids. The compound is available as a United States Pharmacopeia (USP) verified supplement which ensures federally recognized standards for quality and purity (https://www.quality-supplements.org/verified-products/verified-products-listings).

Neuroinflammation

Protandim DRUG

Protandim is an oral tablet derived from five different plants: Silybum marianum (milk thistle), Withania somnifera (Ashwagandha), Camellia sinensis (green tea), Curcuma longa (turmeric) and Bacopa monniera.

Oxidative Stress

Melatonin DRUG

Melatonin is a hormone that has long been known to play a role in regulating sleep. Melatonin supplements are commonly used to treat insomnia, but in recent years, melatonin has been found to play a wider role in human physiology including the potential regulation of autophagy.

Impaired Autophagy and Axonal Transport

MitoQ DRUG

The active ingredient in MitoQ is ubiquinone, the same as found in coenzyme Q10 and idebenone. However, the ubiquinone in MitoQ is attached to a positively charged, lipophilic molecule called TPP (triphenyl phosphonium), which allows it to selectively accumulate in mitochondria. This makes it more potent than untargeted ubiquinone analogs at protecting mitochondria in cultured cells. It can be administered orally and, at least in animals, can cross the blood brain barrier and accumulate in brain mitochondria.

Mitochondrial Dysfunction

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female aged at least 18 years.
• Sporadic or familial ALS diagnosed as per Gold Coast Criteria.
• Patient is able to understand and express informed consent (in the opinion of the site investigator).
• Patient is able to read and write English.
• Patient is expected to survive for the duration of the trial.
• Able to swallow tablets at enrollment and expected to be able to swallow tablets for the duration of the trial.
• Women must not be pregnant (will have evidence of a negative pregnancy test obtained by study team at baseline, or 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.

You may not qualify if:

• Actively or recently (within past 30 days) participating in another intervention trial.
• Currently or recently (within 30 days) taking any of the 4 investigational treatments being used in this trial.
• Prior side effects from any of the 4 investigational treatments being used in this trial.
• 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.

Sponsors & Collaborators

• Duke University: lead
• Temple University: collaborator

Study Sites (2)

Duke University Medical Center

Durham, North Carolina, 27705, United States

Location

Temple University

Philadelphia, Pennsylvania, 19122, United States

Location

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Interventions

astaxanthine; Protandim; Melatonin; mitoquinone

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Tryptamines; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: At month 3, DIGAP classification will be revealed to each participant and based on this, they will receive 1 of 4 treatments. They will take their assigned treatment for 6 months.

Study Record Dates

• First Submitted: April 9, 2024
• First Posted: May 24, 2024
• Study Start: June 12, 2024
• Primary Completion: May 22, 2025
• Study Completion: June 24, 2025
• Last Updated: September 26, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)