Effect of Tarenflurbil on Cognitive Decline and Activities of Daily Living in Patients With Mild Alzheimer Disease<subtitle>A Randomized Controlled Trial</subtitle>
Open accessAbstract
CONTEXT: Amyloid-beta peptide (Abeta(42)) has been implicated in the pathogenesis of Alzheimer disease (AD). Tarenflurbil, a selective Abeta(42)-lowering agent, demonstrated encouraging results on cognitive and functional outcomes among mildly affected patients in an earlier phase 2 trial. OBJECTIVE: To determine the efficacy, safety, and tolerability of tarenflurbil. DESIGN, SETTING, AND PATIENTS: A multicenter, randomized, double-blind, placebo-controlled trial enrolling patients with mild AD was conducted at 133 trial sites in the United States between February 21, 2005, and April 30, 2008. Concomitant treatment with cholinesterase inhibitors or memantine was permitted. INTERVENTION: Tarenflurbil, 800 mg, or placebo, administered twice a day. MAIN OUTCOME MEASURES: Co-primary efficacy end points were the change from baseline to month 18 in total score on the subscale of the Alzheimer Disease Assessment Scale-Cognitive Subscale (ADAS-Cog, 80-point version) and Alzheimer Disease Cooperative Studies-activities of daily living (ADCS-ADL) scale. Additional prespecified slope analyses explored the possibility of disease modification. RESULTS: Of the 1684 participants randomized, 1649 were included in the analysis, and 1046 completed the trial. Tarenflurbil had no beneficial effect on the co-primary outcomes (difference in change from baseline to month 18 vs placebo, based on least squares means: 0.1 for ADAS-Cog; 95% CI, -0.9 to 1.1; P = .86 and -0.5 for ADCS-ADL; 95% CI, -1.9 to 0.9; P = .48) using an intent-to-treat analysis. No significant differences occurred in the secondary outcomes. The ADAS-Cog score decreased by 7.1 points over 18 months. The tarenflurbil group had a small increase in frequency of dizziness, anemia, and infections. CONCLUSION: Tarenflurbil did not slow cognitive decline or the loss of activities of daily living in patients with mild AD. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00105547.
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A phase 3 trial of R-flurbiprofen (tarenflurbil) did not show benefits on cognition or activities of daily living over 18 months.
“Despite promising preclinical data, unfortunately a phase 3 clinical trial did not demonstrate any benefits on cognition or ADLs over the course of 18 months (Green et al., 2009).”
From Alzheimer Disease: An Update on Pathobiology and Treatment Strategies (2019) · cites this paper as Green et al., 2009
A drug intended to modify γ secretase activity failed.
“A drug intended to modify γ secretase activity similarly failed [256].”
From The Alzheimer’s disease mitochondrial cascade hypothesis: progress and perspectives (2014) · cites this paper as [256]
Gintonin, a bioactive glycoprotein, reduces formation of Aβ and improves learning and memory capacity through activation of phosphatidic acid receptors involved in hemolysis.
“Gintonin, a bioactive glycoprotein reduces the formation of A 𝛽, improves learning and memory capacity through the activation of phosphatidic acid receptors involved in hemolysis [26 , 27] .”
From Phytotherapy: A promising approach for the treatment of Alzheimer's disease (2022) · cites this paper as [26]
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- Authors
- Green, R. C.
- Affiliations
- Boston University (US)
- Corresponding author
- Green, Robert C.
- ORCID
- Green, Robert C.
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2009-12-16
- Volume
- 302
- Issue
- 23
- Pages
- 2557
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- PMC
- PMC2902875
- OpenAlex
- W1982816514
- Cited by
- 643
- References
- 44
- Citations by year
- 2026: 11 · 2025: 25 · 2024: 39 · 2023: 22 · 2022: 28 · 2021: 32 · 2020: 43 · 2019: 32 · 2018: 26 · 2017: 40 · 2016: 40 · 2015: 31 · 2014: 44 · 2013: 52 · 2012: 63
- FWCI
- 38.79
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- JAMA (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- University of Pennsylvania
- National Institute for Health and Care Research
- National Institutes of Health (RR00533, HG02213, AG13846)
- National Institute on Aging (P30AG008051, K24AG027841, P50AG005142, P30AG013846, P30-AG13846))
- National Human Genome Research Institute (R01HG002213, R01 HG02213)
- National Center for Research Resources (M01-RR-00533, M01RR000533)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
- Keywords
- Alzheimer's disease, mild Alzheimer disease, cognitive decline, activities of daily living, disease modification, ADAS-Cog, drug safety and efficacy, dizziness, anemia, infection
- MeSH terms
- Activities of Daily Living, Aged, Aged, 80 and over, Alzheimer Disease, Cognition, Cognition Disorders, Double-Blind Method, Enzyme Inhibitors, Female, Flurbiprofen, Humans, Male, Middle Aged, Peptide Fragments, Amyloid beta-Peptides, Amyloid Precursor Protein Secretases
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