## Protocol Section
### Identification Module
**NCT ID:** NCT06429059

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

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

#### Organization Study ID Info
**ID:** Pro00114385
#### Organization
**Class:** OTHER
**Full Name:** Duke University
### Status Module
#### Completion Date
**Date:** 2026-06-01

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-31

**Type:** ESTIMATED

**Last Update Submit Date:** 2024-05-30

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2026-06-01

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-06-01

**Type:** ESTIMATED

**Status Verified Date:** 2024-04

#### Study First Post Date
**Date:** 2024-05-24
**Type:** ACTUAL
**Study First Submit Date:** 2024-04-09
**Study First Submit QC Date:** 2024-05-20
### Sponsor Collaborators Module

#### Collaborators

**Class:** OTHER

**Name:** Temple University

#### Lead Sponsor

**Class:** OTHER

**Name:** Duke University

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** True

**Is US Export:** False

### Description Module

**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.

**Detailed 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.

### Conditions Module

**Conditions:**

- Amyotrophic Lateral Sclerosis ALS

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

**Intervention Model Description:** 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.

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 50

**Type:** ESTIMATED

**Phases:**

- PHASE2

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

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

**Intervention Names:**

- Drug: Astaxanthin

**Label:** Neuroinflammation

**Type:** EXPERIMENTAL

#### Arm Group 2

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

**Intervention Names:**

- Drug: Protandim

**Label:** Oxidative Stress

**Type:** EXPERIMENTAL

#### Arm Group 3

**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.

**Intervention Names:**

- Drug: Melatonin

**Label:** Impaired Autophagy and Axonal Transport

**Type:** EXPERIMENTAL

#### Arm Group 4

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

**Intervention Names:**

- Drug: MitoQ

**Label:** Mitochondrial Dysfunction

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Neuroinflammation

**Description:** 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).

**Name:** Astaxanthin

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- Oxidative Stress

**Description:** 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.

**Name:** Protandim

**Type:** DRUG

#### Intervention 3

**Arm Group Labels:**

- Impaired Autophagy and Axonal Transport

**Description:** 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.

**Name:** Melatonin

**Type:** DRUG

#### Intervention 4

**Arm Group Labels:**

- Mitochondrial Dysfunction

**Description:** 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.

**Name:** MitoQ

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** 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.

**Measure:** ALS Functional Rating Scale, Revised (ALSFRS-R)

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

#### Secondary Outcomes

**Description:** They are neuron-specific components of the cytoskeleton. They exist in heavy, medium, and light chain forms. Neurofilament light chain levels are elevated in the spinal fluid and the blood of patients with ALS and other neurodegenerative diseases, and higher levels predict more severe disease progression. These levels rise dramatically when asymptomatic carriers of ALS-causing genetic mutations begin to convert to an ALS phenotype.

**Measure:** Neurofilament Light Chain levels

**Time Frame:** baseline, month 3, month 5 (2 months into treatment) and month 9 (6 months into treatment)

**Description:** Used to measure neuroinflammation. These are known to be abnormal in patients with ALS, their levels correlate with disease progression and they can be altered by drugs in trials.

**Measure:** Neuroinflammation measured by C-reactive protein (CRP)

**Time Frame:** baseline, 3 months, 5 months and 9 months

**Description:** Used to measure neuroinflammation. These are known to be abnormal in patients with ALS, their levels correlate with disease progression and they can be altered by drugs in trials.

**Measure:** Neuroinflammation measured by monocyte chemoattractant protein-1 (MCP-1)

**Time Frame:** baseline, 3 months, 5 months and 9 months

**Description:** Used to measure neuroinflammation. These are known to be abnormal in patients with ALS, their levels correlate with disease progression and they can be altered by drugs in trials.

**Measure:** Neuroinflammation measured by chitotriosidase (CHIT1)

**Time Frame:** baseline, 3 months, 5 months and 9 months

**Description:** Used to measure oxidative stress.

**Measure:** Oxidative stress measured by total antioxidant capacity (TAC)

**Time Frame:** baseline, 3 months, 5 months and 9 months

**Description:** Uric acid is an antioxidant and levels of uric acid have been reported to be lower in ALS subjects and correlated with progression. It has also been shown to be responsive to treatments in trials

**Measure:** Oxidative stress measured by uric acid levels.

**Time Frame:** baseline, 3 months, 5 months and 9 months

**Description:** To measure impaired autophagy, we will use Beclin-1. This highly conserved eukaryotic protein has a major regulatory role in autophagy. It is a component of the phosphatidylinositol-3-kinase (PI3K) complex which mediates vesicle-trafficking thereby inducing autophagy. Beclin-1 dysfunction has been implicated in many disorders, including cancer and neurodegenerative diseases

**Measure:** Impaired autophagy measured by Beclin-1

**Time Frame:** baseline, 3 months, 5 months and 9 months

**Description:** Compromised mitochondrial oxidative phosphorylation shifts the cellular bioenergetic system to anaerobic respiration and increases the level of lactate. Lactate has been used as a biomarker for mitochondrial disease in many previous studies.

**Measure:** Mitochondrial dysfunction measured by lactate.

**Time Frame:** baseline, 3 months, 5 months and 9 months

### Eligibility Module

**Eligibility Criteria:** 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.

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** rachel.m.ward@duke.edu

**Name:** Michelle ward, RN

**Phone:** 919-613-2681

**Role:** CONTACT

**Contact 2:**

**Email:** hailey.zampa@duke.edu

**Name:** Hailey Zampa

**Phone:** 919-613-2681

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Durham

**Contacts:**

***Contact 1:***

- **Email:** rachel.m.ward@duke.edu

- **Name:** Michelle Ward, RN

- **Phone:** 919-613-2681

- **Role:** CONTACT

***Contact 2:***

- **Name:** Richard Bedlack, MD, PhD

- **Role:** PRINCIPAL_INVESTIGATOR

**Country:** United States

**Facility:** Duke University Medical Center

**State:** North Carolina

**Zip:** 27705

**Location 2:**

**City:** Philadelphia

**Contacts:**

***Contact 1:***

- **Email:** john.furey0001@temple.edu

- **Name:** John Furey

- **Role:** CONTACT

***Contact 2:***

- **Email:** christopher.pizzica@temple.edu

- **Name:** Christopher Pizzica

- **Role:** CONTACT

***Contact 3:***

- **Name:** Terry Heiman-Patterson, MD

- **Role:** PRINCIPAL_INVESTIGATOR

**Country:** United States

**Facility:** Temple University

**State:** Pennsylvania

**Zip:** 19122

### IPD Sharing Statement Module

**IPD Sharing:** NO

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000019636

- Term: Neurodegenerative Diseases

- ID: D000009422

- Term: Nervous System Diseases

- ID: D000009468

- Term: Neuromuscular Diseases

- ID: D000013118

- Term: Spinal Cord Diseases

- ID: D000002493

- Term: Central Nervous System Diseases

- ID: D000057177

- Term: TDP-43 Proteinopathies

- ID: D000057165

- Term: Proteostasis Deficiencies

- ID: D000008659

- Term: Metabolic Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: All

- Name: All Conditions

- Abbrev: BC10

- Name: Nervous System Diseases

- Abbrev: BC18

- Name: Nutritional and Metabolic Diseases

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M15415

- Name: Sclerosis

- Relevance: LOW

- As Found: Unknown

- ID: M18879

- Name: Motor Neuron Disease

- Relevance: HIGH

- As Found: Lateral Sclerosis

- ID: M4024

- Name: Amyotrophic Lateral Sclerosis

- Relevance: HIGH

- As Found: Amyotrophic Lateral Sclerosis

- ID: M21558

- Name: Neurodegenerative Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M12411

- Name: Neuromuscular Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M15915

- Name: Spinal Cord Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M5742

- Name: Central Nervous System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M28759

- Name: TDP-43 Proteinopathies

- Relevance: LOW

- As Found: Unknown

- ID: M28747

- Name: Proteostasis Deficiencies

- Relevance: LOW

- As Found: Unknown

- ID: M11639

- Name: Metabolic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: T349

- Name: Amyotrophic Lateral Sclerosis

- Relevance: HIGH

- As Found: Amyotrophic Lateral Sclerosis

- ID: T4699

- Name: Primary Lateral Sclerosis

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000016472

- Term: Motor Neuron Disease

- ID: D000000690

- Term: Amyotrophic Lateral Sclerosis

### Intervention Browse Module - Ancestors

- ID: D000000975

- Term: Antioxidants

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

- ID: D000020011

- Term: Protective Agents

- ID: D000045505

- Term: Physiological Effects of Drugs

- ID: D000002492

- Term: Central Nervous System Depressants

### Intervention Browse Module - Browse Branches

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: Micro

- Name: Micronutrients

- Abbrev: CNSDep

- Name: Central Nervous System Depressants

- Abbrev: HB

- Name: Herbal and Botanical

- Abbrev: Ot

- Name: Other Dietary Supplements

### Intervention Browse Module - Browse Leaves

- ID: M9789

- Name: Hormones

- Relevance: LOW

- As Found: Unknown

- ID: M17201

- Name: Ubiquinone

- Relevance: LOW

- As Found: Unknown

- ID: M271049

- Name: Coenzyme Q10

- Relevance: LOW

- As Found: Unknown

- ID: M11533

- Name: Melatonin

- Relevance: HIGH

- As Found: Profile

- ID: M342247

- Name: Turmeric extract

- Relevance: LOW

- As Found: Unknown

- ID: M5592

- Name: Carotenoids

- Relevance: LOW

- As Found: Unknown

- ID: M273909

- Name: Idebenone

- Relevance: LOW

- As Found: Unknown

- ID: M4292

- Name: Antioxidants

- Relevance: LOW

- As Found: Unknown

- ID: M21869

- Name: Protective Agents

- Relevance: LOW

- As Found: Unknown

- ID: T244

- Name: Orange

- Relevance: LOW

- As Found: Unknown

- ID: T383

- Name: Coenzyme Q10

- Relevance: LOW

- As Found: Unknown

- ID: T410

- Name: Melatonin

- Relevance: HIGH

- As Found: Profile

- ID: T229

- Name: Milk Thistle

- Relevance: LOW

- As Found: Unknown

- ID: T319

- Name: Turmeric

- Relevance: LOW

- As Found: Unknown

- ID: T312

- Name: Tea

- Relevance: LOW

- As Found: Unknown

- ID: T407

- Name: Lutein

- Relevance: LOW

- As Found: Unknown

- ID: T61

- Name: Ashwagandha

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000008550

- Term: Melatonin

### Misc Info Module

- Version Holder: 2024-05-31
