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| Name | Class |
|---|---|
| Temple University | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Neuroinflammation | Experimental | Study participants in this category are expected to have inflammation in their brains and spinal cords. |
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| Oxidative Stress | Experimental | Study participants in this category are expected to have too many damaging "free radical" chemicals in their brains and spinal cords. |
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| 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. |
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| Mitochondrial Dysfunction | Experimental | Study participants in this category are expected to have motor neurons that are unable to produce normal amounts of energy. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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). |
| Measure | Description | Time Frame |
|---|---|---|
| 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) |
| Measure | Description | Time Frame |
|---|---|---|
| Neurofilament Light Chain levels | 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Duke University Medical Center | Durham | North Carolina | 27705 | United States | ||
| Temple University |
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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.
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| 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. |
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| 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. |
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| 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. |
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| baseline, month 3, month 5 (2 months into treatment) and month 9 (6 months into treatment) |
| Neuroinflammation measured by C-reactive protein (CRP) | 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. | baseline, 3 months, 5 months and 9 months |
| Neuroinflammation measured by monocyte chemoattractant protein-1 (MCP-1) | 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. | baseline, 3 months, 5 months and 9 months |
| Neuroinflammation measured by chitotriosidase (CHIT1) | 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. | baseline, 3 months, 5 months and 9 months |
| Oxidative stress measured by total antioxidant capacity (TAC) | Used to measure oxidative stress. | baseline, 3 months, 5 months and 9 months |
| Oxidative stress measured by uric acid levels. | 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 | baseline, 3 months, 5 months and 9 months |
| Impaired autophagy measured by Beclin-1 | 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 | baseline, 3 months, 5 months and 9 months |
| Mitochondrial dysfunction measured by lactate. | 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. | baseline, 3 months, 5 months and 9 months |
| Philadelphia |
| Pennsylvania |
| 19122 |
| United States |
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| Release Date | Unrelease Date | Unrelease Date Unknown | Reset Date | MCP Release Number |
|---|---|---|---|---|
| May 22, 2026 | Jun 17, 2026 | 6 | ||
| Jun 30, 2026 |
| ID | Term |
|---|---|
| D000690 | Amyotrophic Lateral Sclerosis |
| ID | Term |
|---|---|
| D013118 | Spinal Cord Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D016472 | Motor Neuron Disease |
| D019636 | Neurodegenerative Diseases |
| D057177 | TDP-43 Proteinopathies |
| D009468 | Neuromuscular Diseases |
| D057165 | Proteostasis Deficiencies |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| C005948 | astaxanthine |
| C509374 | Protandim |
| D008550 | Melatonin |
| C429014 | mitoquinone |
| ID | Term |
|---|---|
| D014363 | Tryptamines |
| D007211 | Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
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