Allopregnanolone Regenerative Therapeutic for Mild Alzheimer's Disease

NCT04838301 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: Allo-20-001R01AG063826
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 10

Brief Summary

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.

Conditions

Alzheimer Dementia; Late Onset Alzheimer Disease; Neurodegenerative Diseases

Keywords

Mild Alzheimer Disease; Regenerative Therapeutic; Neurogenesis; Allopregnanolone

Outcome Measures

Primary Outcomes (1)

• Hippocampal volume

  mm3

  Baseline to 6 months

Secondary Outcomes (5)

• Cambridge Cognition's Paired Associates Learning Test

  Baseline to 6 months

• Cambridge Neuropsychological Test Automated Battery (CANTAB)

  Baseline to 6 months

• Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) 11

  Baseline to 6 months

• Alzheimer's Disease Cooperative Study (ADCS) Instrumental Activities of Daily (iADL) Living (iADL)

  Baseline to 6 months

• Safety and tolerability

  Baseline to 6 months

Other Outcomes (12)

• Other regional brain volumes

  Baseline to 6 and 9 months

• Diffusion tensor imaging (DTI)

  Baseline to 6 and 9 months

• Resting state functional MRI

  Baseline to 6 and 9 months

Study Arms (2)

Allo group

EXPERIMENTAL

Allopregnanolone 4mg IV 30-minute infusion once per week for 6 months.

Drug: Allopregnanolone

Control group

PLACEBO COMPARATOR

Placebo (normal saline) IV 30-minute infusion once per week for 6 months.

Other: Placebo

Interventions

Allopregnanolone DRUG

Allopregnanolone 4mg IV via 30-minute infusion, once per week.

Also known as: Allo

Allo group

Placebo OTHER

Normal saline solution IV via 30-minute infusion, once per week

Control group

Eligibility Criteria

• Age: 55 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Arizona: lead
• Syneos Health: collaborator
• University of Southern California: collaborator
• ADM Diagnostics: collaborator
• National Institute on Aging (NIA): collaborator

Study Sites (10)

Perseverance Research Center

Scottsdale, Arizona, 85253, United States

RECRUITING

University of Arizona / Clinical & Translational Sciences Research Center

Tucson, Arizona, 85721, United States

RECRUITING

ATP Clinical Research

Costa Mesa, California, 92626, United States

RECRUITING

Wake Research-PRI, LLC

Los Alamitos, California, 90720, United States

WITHDRAWN

Syrentis Clinical Research

Santa Ana, California, 92705, United States

TERMINATED

Optimus U Corporation

Miami, Florida, 33135, United States

RECRUITING

Miami Jewish Health

Miami, Florida, 33137, United States

RECRUITING

Combined Research Orlando

Orlando, Florida, 32807, United States

TERMINATED

Conquest Research

Winter Park, Florida, 32789, United States

RECRUITING

MedVadis Research

Waltham, Massachusetts, 02451, United States

RECRUITING

Related Publications (4)

• 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.

  PMID: 35310526 BACKGROUND

• 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.

  PMID: 33344752 BACKGROUND

• 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.

  PMID: 23438839 BACKGROUND

• 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.

  PMID: 16842093 BACKGROUND

MeSH Terms

Conditions

Alzheimer Disease; Neurodegenerative Diseases

Interventions

Pregnanolone

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Roberta D Brinton, PhD

  University of Arizona

  PRINCIPAL INVESTIGATOR

• Lon Schneider, MD

  University of Southern California

  PRINCIPAL INVESTIGATOR

• Gerson D Hernandez, MD, MPH

  University of Arizona

  STUDY DIRECTOR

Central Study Contacts

Claudia M Lopez, BS

CONTACT

520-626-6276; claudiml@arizona.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: After 6 months participants and study personnel will be aware of the open label phase, but initial randomization will remain blind during the entire length of the study (placebo-controlled and open-label periods); that is, all participants and study personnel are blinded to each participant's randomization to initial treatment group.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Center for Innovation in Brain Science; Professor, Departments of Pharmacology and Neurology

Model Details: Participants are assigned to the active intervention or placebo in parallel for 12 months. After 12 months, all participants in the placebo group will be crossed-over to receive Allo for the remainder of the study (6 month open-label phase).

Study Record Dates

• First Submitted: March 25, 2021
• First Posted: April 9, 2021
• Study Start: August 15, 2023
• Primary Completion (Estimated): November 18, 2026
• Study Completion (Estimated): March 18, 2027
• Last Updated: March 13, 2026

Record last verified: 2026-03

Locations

US (10)