ArticleAlzheimer's & dementia (New York, N. Y.)2020
Safety, tolerability, and pharmacokinetics of allopregnanolone as a regenerative therapeutic for Alzheimer's disease: A single and multiple ascending dose phase 1b/2a clinical trial.
Article in Alzheimer's & dementia (New York, N. Y.), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 17 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.
Allopregnanolone Regenerative Therapeutic for MCI/AD: Dose Finding Phase 1
Safety and Efficacy of Allopregnanolone (Allo) as a Regenerative Therapeutic for Alzheimer's Disease: Multicenter, Double-Blind, Randomized, Placebo-Controlled, Phase 2 Clinical Trial
Who cites it
17 citing papers in PubMed, 32 citations in OpenAlex.
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- Integrative multiomics reveals common endotypes across PSEN1, PSEN2, and APP mutations in familial Alzheimer's disease.Alzheimer's research & therapy · 2025Article
- Emerging Pro-neurogenic Therapeutic Strategies for Neurodegenerative Diseases: A Review of Pre-clinical and Clinical Research.Molecular neurobiology · 2025Review
- Neuroactive Steroids, Toll-like Receptors, and Neuroimmune Regulation: Insights into Their Impact on Neuropsychiatric Disorders.Life (Basel, Switzerland) · 2024Review
- Characterization of age- and stage-dependent impaired adult subventricular neurogenesis in 5XFAD mouse model of Alzheimer's disease.BMB reports · 2023Article
- Article
- Allopregnanolone: Regenerative therapeutic to restore neurological health.Neurobiology of stress · 2022Article
- GABAkines - Advances in the discovery, development, and commercialization of positive allosteric modulators of GABAPharmacology & therapeutics · 2022Review
- Evaluation of mild cognitive impairment genetic susceptibility risks in a Chinese population.BMC psychiatry · 2022Article
- Development of neuroactive steroids for the treatment of postpartum depression.Journal of neuroendocrinology · 2022Review
- Allopregnanolone: An overview on its synthesis and effects.Journal of neuroendocrinology · 2022Review
- Allopregnanolone and neuroHIV: Potential benefits of neuroendocrine modulation in the era of antiretroviral therapy.Journal of neuroendocrinology · 2022Review
- Progesterone and Allopregnanolone Neuroprotective Effects in the Wobbler Mouse Model of Amyotrophic Lateral Sclerosis.Cellular and molecular neurobiology · 2022Review
- Exploratory imaging outcomes of a phase 1b/2a clinical trial of allopregnanolone as a regenerative therapeutic for Alzheimer's disease: Structural effects and functional connectivity outcomes.Alzheimer's & dementia (New York, N. Y.) · 2022Article
- Safety, tolerability, and pharmacokinetics of allopregnanolone as a regenerative therapeutic for Alzheimer's disease: A single and multiple ascending dose phase 1b/2a clinical trial.Alzheimer's & dementia (New York, N. Y.) · 2020Article
Corrections and comments
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Authors and funding
16 authors at 7 institutions in 2 countries.
Funding
Abstract
introductionAllopregnanolone is an endogenous neurosteroid with the potential to be a novel regenerative therapeutic for Alzheimer's disease (AD). Foundations of mechanistic understanding and well-established preclinical safety efficacy make it a viable candidate.
methodsA randomized, double-blinded, placebo-controlled, single and multiple ascending dose trial was conducted. Intravenous allopregnanolone or placebo was administered once-per-week for 12 weeks with a 1-month follow-up. Participants with early AD (mild cognitive impairment due to AD or mild AD), a Mini-Mental State Examination score of 20-26 inclusive, and age ≥55 years were randomized (6:2 to three allopregnanolone dosing cohorts or one placebo cohort). Primary endpoint was safety and tolerability. Secondary endpoints included pharmacokinetic (PK) parameters and maximally tolerated dose (MTD). Exploratory endpoints included cognitive and imaging biomarkers.
resultsA total of 24 participants completed the trial. Allopregnanolone was safe and well tolerated in all study participants. No differences were observed between treatment arms in the occurrence and severity of adverse events (AE). Most common AE were mild to moderate in severity and included rash (n = 4 [22%]) and fatigue (n = 3 [17%]). A single non-serious AE, dizziness, was attributable to treatment. There was one serious AE not related to treatment. Pharmacokinetics indicated a predictable linear dose-response in plasma concentration of allopregnanolone after intravenous administration over 30 minutes. The maximum plasma concentrations for the 2 mg, 4 mg, 6 mg, and 10 mg dosages were 14.53 ng/mL (+/-7.31), 42.05 ng/mL (+/-14.55), 60.07 ng/mL (+/-12.8), and 137.48 ng/mL (+/-38.69), respectively. The MTD was established based on evidence of allopregnanolone-induced mild sedation at the highest doses; a sex difference in the threshold for sedation was observed (males 10 mg; females 14 mg). No adverse outcomes on cognition or magnetic resonance imaging-based imaging outcomes were evident.
conclusionsAllopregnanolone was well tolerated and safe across all doses in persons with early AD. Safety, MTD, and PK profiles support advancement of allopregnanolone as a regenerative therapeutic for AD to a phase 2 efficacy trial.
trial registrationClinicalTrials.gov-NCT02221622.
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Registered trials
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 OpenQuestion graph.