Allopregnanolone Regenerative Therapeutic for Mild Alzheimer's Disease (REGEN-BRAIN©)

Safety and Efficacy of Allopregnanolone (Allo) as a Regenerative Therapeutic for Alzheimer's Disease: Multicenter, Double-Blind, Randomized, Placebo-Controlled, Phase 2 Clinical Trial

A phase 2, double-blind, randomized, placebo-controlled clinical trial to evaluate the safety and efficacy of Allopregnanolone as a regenerative therapeutic for Alzheimer's disease.

Study Overview

• Status: Recruiting
• Conditions: Neurodegenerative Diseases; Alzheimer Dementia; Late Onset Alzheimer Disease
• Intervention / Treatment: Drug: Allopregnanolone; Other: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Claudia M Lopez, BS; Phone Number: 520-626-6276; Email: claudiml@arizona.edu

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85253
      • Recruiting
      • Perseverance Research Center
      • Principal Investigator: Allan Block, MD
      • Contact: Nicole Hank, PhD; Phone Number: 4804716132
    • Tucson, Arizona, United States, 85721
      • Recruiting
      • University of Arizona / Clinical & Translational Sciences Research Center
      • Principal Investigator: David Labiner, MD
      • Contact: Faten Sebaali; Phone Number: 520-626-3576; Email: fsebaali@arizona.edu
      • Contact: Dakota Darby; Phone Number: 520-626-4718; Email: dakotadarby@arizona.edu
      • Sub-Investigator: Firas Kaddouh, MD
  • California
    • Costa Mesa, California, United States, 92626
      • Recruiting
      • ATP Clinical Research
      • Principal Investigator: Gustavo Alva, MD
      • Contact: Bobby Shih; Phone Number: 714-277-4472
      • Contact: Caitlyn Villanueva; Phone Number: 714-277-4472
    • Los Alamitos, California, United States, 90720
      • Withdrawn
      • Wake Research-PRI, LLC
    • Santa Ana, California, United States, 92705
      • Terminated
      • Syrentis Clinical Research
  • Florida
    • Miami, Florida, United States, 33137
      • Recruiting
      • Miami Jewish Health
      • Contact: Mariolga Aymat; Phone Number: 64103 305-751-8626
      • Contact: Alexander Gomez; Phone Number: 64199 305-751-8626
      • Principal Investigator: Marc E Agronin, MD
    • Miami, Florida, United States, 33135
      • Recruiting
      • Optimus U Corporation
      • Contact: Yaneicy Gonazalez Rojas, MD
      • Principal Investigator: Yaneicy Gonazalez Rojas, MD
    • Orlando, Florida, United States, 32807
      • Terminated
      • Combined Research Orlando
    • Winter Park, Florida, United States, 32789
      • Recruiting
      • Conquest Research
      • Principal Investigator: Rekha Gandhi, MD
      • Contact: Melissa O'Neill; Phone Number: 407-916-0060
      • Contact: Rathod Meera; Phone Number: 407-916-0060
  • Massachusetts
    • Waltham, Massachusetts, United States, 02451
      • Recruiting
      • MedVadis Research
      • Contact: Donald Counihan; Phone Number: 781-373-2940
      • Contact: Jessica O'Brien; Phone Number: 781-373-2940
      • Principal Investigator: David J DiBenedetto, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 51 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Allo group; Allopregnanolone 4mg IV 30-minute infusion once per week for 6 months.	Drug: Allopregnanolone; Allopregnanolone 4mg IV via 30-minute infusion, once per week.; Other Names: Allo
Placebo Comparator: Control group; Placebo (normal saline) IV 30-minute infusion once per week for 6 months.	Other: Placebo; Normal saline solution IV via 30-minute infusion, once per week

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hippocampal volume	mm3	Baseline to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cambridge Cognition's Paired Associates Learning Test	Total errors score (adjusted) - number of errors made by the participant (range: 0 to ~120). Higher scores indicate poor performance.	Baseline to 6 months
Cambridge Neuropsychological Test Automated Battery (CANTAB)	Composite score (higher score indicate better outcome)	Baseline to 6 months
Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) 11	Total score (range 0 to 70); higher scores indicate poor performance.	Baseline to 6 months
Alzheimer's Disease Cooperative Study (ADCS) Instrumental Activities of Daily (iADL) Living (iADL)	iADL subscore (range 0-56): Lower score indicates greater severity	Baseline to 6 months
Safety and tolerability	Frequency of adverse events and serious adverse events	Baseline to 6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Other regional brain volumes	Change in regional brain volumes (mm3)	Baseline to 6 and 9 months
Diffusion tensor imaging (DTI)	Change in white matter tract diffusion (scalar values and/or mm2/sec)	Baseline to 6 and 9 months
Resting state functional MRI	Change in functional connectivity (z transformed correlations)	Baseline to 6 and 9 months
Arterial spin labeling (ASL)	Change in regional cerebral blood flow (mL/100g)	Baseline to 6 and 9 months
Exploratory blood based biomarkers	Change from baseline in biomarkers of AD pathology, neurogenesis and inflammation	Baseline to 6 and 9 months
Clinical Dementia Rating (CDR)	Sum of boxes score (CDR-SB): range 0-18	Baseline to 6 and 9 months
Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) 14	Total score (range 0-90)	Baseline to 6 and 9 months
Mini Mental State Examination (MMSE)	Total score (range 0-30)	Baseline to 6 and 9 months
Neuropsychiatric Inventory-Questionnaire (NPI-Q)	Total score (range 0-36). Higher scores indicate greater symptom severity	Baseline to 6 and 9 months
EuroQol 5-Dimension / 5-Level health-related quality of life scale scores (EQ-5D-5L)	Reported as frequency, percentage and index value.	Baseline to 6 and 9 months
Quality of Life in Alzheimer's Disease scale (QoL-AD)	Total score (range 13-52). Higher score indicate better QoL	Baseline to 6 and 9 months
Zarit Burden Interview (ZBI)	Total score (range 0-48). Higher scores indicate high burden	Baseline to 6 and 9 months

Collaborators and Investigators

• Sponsor: University of Arizona
• Collaborators: National Institute on Aging (NIA); University of Southern California; Syneos Health; ADM Diagnostics
• Investigators: Principal Investigator: Roberta D Brinton, PhD, University of Arizona; Principal Investigator: Lon Schneider, MD, University of Southern California; Study Director: Gerson D Hernandez, MD, MPH, University of Arizona

Publications and helpful links

General Publications

• Hernandez GD, Solinsky CM, Mack WJ, Kono N, Rodgers KE, Wu CY, Mollo AR, Lopez CM, Pawluczyk S, Bauer G, Matthews D, Shi Y, Law M, Rogawski MA, Schneider LS, Brinton RD. 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. Alzheimers Dement (N Y). 2020 Dec 16;6(1):e12107. doi: 10.1002/trc2.12107. eCollection 2020.
• Brinton RD. Neurosteroids as regenerative agents in the brain: therapeutic implications. Nat Rev Endocrinol. 2013 Apr;9(4):241-50. doi: 10.1038/nrendo.2013.31. Epub 2013 Feb 26.
• Brinton RD, Wang JM. Therapeutic potential of neurogenesis for prevention and recovery from Alzheimer's disease: allopregnanolone as a proof of concept neurogenic agent. Curr Alzheimer Res. 2006 Jul;3(3):185-90. doi: 10.2174/156720506777632817.
• Raikes AC, Hernandez GD, Matthews DC, Lukic AS, Law M, Shi Y, Schneider LS, Brinton RD. 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. Alzheimers Dement (N Y). 2022 Mar 14;8(1):e12258. doi: 10.1002/trc2.12258. eCollection 2022.

Study record dates

Study Major Dates

• Study Start (Actual): August 15, 2023
• Primary Completion (Estimated): November 18, 2026
• Study Completion (Estimated): March 18, 2027

Study Registration Dates

• First Submitted: March 25, 2021
• First Submitted That Met QC Criteria: April 6, 2021
• First Posted (Actual): April 9, 2021

Study Record Updates

• Last Update Posted (Actual): March 13, 2026
• Last Update Submitted That Met QC Criteria: March 11, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Neurogenesis; Allopregnanolone; Mild Alzheimer Disease; Regenerative Therapeutic
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Neurocognitive Disorders; Dementia; Tauopathies; Alzheimer Disease; Neurodegenerative Diseases; Polycyclic Compounds; Pregnanes; Steroids; Fused-Ring Compounds; Pregnanolone
• Other Study ID Numbers: Allo-20-001; R01AG063826 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No