Trial reportTranslational neurodegeneration2023
Combined metabolic activators improve cognitive functions in Alzheimer's disease patients: a randomised, double-blinded, placebo-controlled phase-II trial.
Trial report in Translational neurodegeneration, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04044131 (A Phase 2, Randomized, Placebo Controlled Study to Evaluate the Efficacy, Tolerability and Safety of Metabolic Cofactor Supplementation in Alzheimer's Disease), which is not on this map. Cited by 54 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase 2, Randomized, Placebo Controlled Study to Evaluate the Efficacy, Tolerability and Safety of Metabolic Cofactor Supplementation in Alzheimer's Disease (AD) And Parkinson's Disease (PD) Patients
Who cites it
54 citing papers in PubMed, 72 citations in OpenAlex.
- Multi-omics characterization of improved cognitive functions in Parkinson's disease patients after the combined metabolic activator treatment: a randomized, double-blinded, placebo-controlled phase II trial.Brain communications · 2025Trial
- AST-001 versus placebo for social communication in children with autism spectrum disorder: A randomized clinical trial.Psychiatry and clinical neurosciences · 2025Trial
- Combined metabolic activators therapy ameliorates liver fat in nonalcoholic fatty liver disease patients.Molecular systems biology · 2021Trial
- Breaking the age-related redox spiral for regeneration.Neural regeneration research · 2026Article
- Ferroptosis and aging: Inducing and catalyzing neurodegenerative diseases.Neural regeneration research · 2026Article
- A combined artificial intelligence-wet lab approach identifies a pivotal role of the NADAlzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- NADAlzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Organelle resilience as a comparative blueprint for longevity.EMBO molecular medicine · 2026Review
- Dietary Bioactives in Alzheimer's Disease: A Critical Appraisal of Clinical Trials and Future Nutritional Strategies.Nutrients · 2026Review
- Article
- Redox therapy for neuropsychiatric disorders: Molecular mechanisms and biomarker development.Science advances · 2026Review
- Article
- Aging at the Crossroads of Cuproptosis and Ferroptosis: From Molecular Pathways to Age-Related Pathologies and Therapeutic Perspectives.International journal of molecular sciences · 2026Review
- Administration of bifidobacteria and dietary fiber improves cognitive function by increasing short-chain fatty acid-producing bacteria and reducing inflammation.Bioscience of microbiota, food and health · 2026Article
- Advances in the treatment of Alzheimer's disease.Frontiers in pharmacology · 2026Review
- Peptidylarginine Deiminases: An Overview of Recent Advances in Citrullination Research.International journal of molecular sciences · 2025Review
- Review
- Immunosenescence in aging and neurodegenerative diseases: evidence, key hallmarks, and therapeutic implications.Translational neurodegeneration · 2025Review
- Perspectives on Alzheimer's Disease Treatment Based on Counteracting Oxidative Stress.Biomolecules · 2025Review
- Emerging strategies, applications and challenges of targeting NADNature aging · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
27 authors at 10 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAlzheimer's disease (AD) is associated with metabolic abnormalities linked to critical elements of neurodegeneration. We recently administered combined metabolic activators (CMA) to the AD rat model and observed that CMA improves the AD-associated histological parameters in the animals. CMA promotes mitochondrial fatty acid uptake from the cytosol, facilitates fatty acid oxidation in the mitochondria, and alleviates oxidative stress.
methodsHere, we designed a randomised, double-blinded, placebo-controlled phase-II clinical trial and studied the effect of CMA administration on the global metabolism of AD patients. One-dose CMA included 12.35 g L-serine (61.75%), 1 g nicotinamide riboside (5%), 2.55 g N-acetyl-L-cysteine (12.75%), and 3.73 g L-carnitine tartrate (18.65%). AD patients received one dose of CMA or placebo daily during the first 28 days and twice daily between day 28 and day 84. The primary endpoint was the difference in the cognitive function and daily living activity scores between the placebo and the treatment arms. The secondary aim of this study was to evaluate the safety and tolerability of CMA. A comprehensive plasma metabolome and proteome analysis was also performed to evaluate the efficacy of the CMA in AD patients.
resultsWe showed a significant decrease of AD Assessment Scale-cognitive subscale (ADAS-Cog) score on day 84 vs day 0 (P = 0.00001, 29% improvement) in the CMA group. Moreover, there was a significant decline (P = 0.0073) in ADAS-Cog scores (improvement of cognitive functions) in the CMA compared to the placebo group in patients with higher ADAS-Cog scores. Improved cognitive functions in AD patients were supported by the relevant alterations in the hippocampal volumes and cortical thickness based on imaging analysis. Moreover, the plasma levels of proteins and metabolites associated with NAD + and glutathione metabolism were significantly improved after CMA treatment.
conclusionOur results indicate that treatment of AD patients with CMA can lead to enhanced cognitive functions and improved clinical parameters associated with phenomics, metabolomics, proteomics and imaging analysis. Trial registration ClinicalTrials.gov NCT04044131 Registered 17 July 2019, https://clinicaltrials.gov/ct2/show/NCT04044131.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.