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

Duke University

Status and phase: Active, not recruiting; Phase 2

Conditions: Amyotrophic Lateral Sclerosis ALS

Treatments: Drug: Melatonin; Drug: Astaxanthin; Drug: MitoQ; Drug: Protandim

Study type: Interventional

Funder types: Other

Identifiers

NCT06429059

Pro00114385

Details and patient eligibility

About

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.

Full description

This will be a widely inclusive, largely remote/virtual, two-center, open-label pilot trial utilizing 50 participants as their own controls. Following informed consent and screening, participants will provide demographics, disease characteristics, co-morbidities, and concomitant medications. They will have a baseline ALSFRS-R score obtained and blood will be drawn for DIGAP classification, PBMCs (which will be used to generate iPSCs from which motor neurons and/or microglia can be generated), baseline mechanistic biomarkers and baseline neurofilament light chain. A urine pregnancy test will be obtained for pre-menopausal females who have not had one by their own doctor in the past 7 days. Each month after that, they will be contacted by phone by study coordinators to review adverse events, new co-morbidities, and concomitant medications, and to generate a new ALSFRS-R score. 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. At months 3, 5 and 9 they will be asked to return for in person blood draws for repeat mechanistic biomarkers and neurofilament light chain measurements. All of the described blood tests and investigational treatments are being performed exclusively for research purposes.

Enrollment: 50 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Male or female aged at least 18 years.
2. Sporadic or familial ALS diagnosed as per Gold Coast Criteria.
3. Patient is able to understand and express informed consent (in the opinion of the site investigator).
4. Patient is able to read and write English.
5. Patient is expected to survive for the duration of the trial.
6. Able to swallow tablets at enrollment and expected to be able to swallow tablets for the duration of the trial.
7. 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)
8. 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

1. Actively or recently (within past 30 days) participating in another intervention trial.
2. Currently or recently (within 30 days) taking any of the 4 investigational treatments being used in this trial.
3. Prior side effects from any of the 4 investigational treatments being used in this trial.
4. 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.
5. Pregnant women or women currently breastfeeding.
6. Life expectancy shorter than the duration of the trial.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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50 participants in 4 patient groups

Neuroinflammation

Experimental group

Description:

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

Treatment:

Drug: Astaxanthin

Oxidative Stress

Experimental group

Description:

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

Treatment:

Drug: Protandim

Impaired Autophagy and Axonal Transport

Experimental group

Description:

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.

Treatment:

Drug: Melatonin

Mitochondrial Dysfunction

Experimental group

Description:

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

Treatment:

Drug: MitoQ