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Allopregnanolone Regenerative Therapeutic for Mild Alzheimer's Disease

NCT04838301 · University of Arizona
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Official title
Safety and Efficacy of Allopregnanolone (Allo) as a Regenerative Therapeutic for Alzheimer's Disease: Multicenter, Double-Blind, Randomized, Placebo-Controlled, Phase 2 Clinical Trial
About this study
This is a proof-of-concept phase 2 clinical trial to investigate the long-term safety and efficacy of Allo to function as a regenerative therapeutic to restore structural integrity and cognitive function of the brain in participants with mild Alzheimer's disease (AD) dementia. Study participants will be male and female, diagnosed with probable AD, Mini-Mental State Exam (MMSE) 20 to 26, ages 55 to 80 years old. After a 2-4-week screening period, participants will be randomized to 4 mg Allo (administered intravenously over 30 minutes, once per week, in clinic) or matching placebo, 1:1 allocation, for a period of 6 months. After 6 months, all participants in the placebo group will be crossed-over to receive Allo for the remainder of the study (3 month open-label phase). Brain imaging to evaluate the primary endpoint will be conducted at baseline, 3 and 6 months.
Eligibility criteria
Main Inclusion Criteria: * Men and postmenopausal women * Age 55 to 80 years old * Meets NIA-AA criteria for probable AD dementia * MMSE of 20-26 * Plasma p-Tau217 positive * Geriatric Depression Scale short form (GDS-S) score of ≤ 6 * No medical contraindications to participation * Capacity to provide informed consent at screening Main Exclusion Criteria: * Dementia other than probable AD * Use of benzodiazepines, anticonvulsants, antipsychotics, or other drugs that might interact with the GABA-A receptor complex * History of stroke with a modified Hachinski Ischemic Scale score \>4 * History of seizure disorder, focal brain lesion, traumatic brain injury * History within the last 5 years of a primary or recurrent malignant disease * Unstable or clinically significant cardiovascular, kidney or liver disease * MRI indicative of any other significant abnormality, including but not limited to one or more significant ARIA-E or macro-hemorrhage findings, or multiple microhemorrhages (\>8), or Fazekas score of 3; encephalomalacia, aneurysms, vascular malformations, subdural hematoma, or space occupying lesions * Any conditions that would contraindicate MRI studies. * No evidence of AD-like pattern of brain atrophy
Study design
Enrollment target: 100 participants
Allocation: randomized
Masking: quadruple
Age groups: adult, older_adult
Timeline
Starts: 2023-08-15
Estimated completion: 2027-03-18
Last updated: 2026-03-13
Interventions
Drug: AllopregnanoloneOther: Placebo
Primary outcomes
  • Hippocampal volume (Baseline to 6 months)
Sponsor
University of Arizona · other
With: National Institute on Aging (NIA), Syneos Health, University of Southern California, ADM Diagnostics
Contacts & investigators
ContactClaudia M Lopez, BS · contact · claudiml@arizona.edu · 520-626-6276
InvestigatorRoberta D Brinton, PhD · principal_investigator, University of Arizona
InvestigatorLon Schneider, MD · principal_investigator, University of Southern California
InvestigatorGerson D Hernandez, MD, MPH · study_director, University of Arizona
All locations (10)
Perseverance Research CenterRecruiting
Scottsdale, Arizona, United States
University of Arizona / Clinical & Translational Sciences Research CenterRecruiting
Tucson, Arizona, United States
ATP Clinical ResearchRecruiting
Costa Mesa, California, United States
Wake Research-PRI, LLCWithdrawn
Los Alamitos, California, United States
Syrentis Clinical ResearchTerminated
Santa Ana, California, United States
Optimus U CorporationRecruiting
Miami, Florida, United States
Miami Jewish HealthRecruiting
Miami, Florida, United States
Combined Research OrlandoTerminated
Orlando, Florida, United States
Conquest ResearchRecruiting
Winter Park, Florida, United States
MedVadis ResearchRecruiting
Waltham, Massachusetts, United States
Allopregnanolone Regenerative Therapeutic for Mild Alzheimer's Disease · TrialPath