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NCT Number: NCT04838301

Allopregnanolone Regenerative Therapeutic for Mild Alzheimer's Disease

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.

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This study is active but is not currently recruiting participants.

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Key information

Conditions

Alzheimer Dementia Alzheimer Disease Brain Diseases Central Nervous System Diseases Dementia Late Onset Alzheimer Disease Mental Disorders Nervous System Diseases Neurocognitive Disorders Neurodegenerative Diseases Tauopathies

Age range

55 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Perseverance Research Center, Scottsdale, Arizona, United States

Loading trial locations.

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Allopregnanolone

Drug

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

Other names: Allo

Placebo

Other

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

Primary outcomes

  1. Hippocampal volume

    Time frame: Baseline to 6 months

    mm3

Secondary outcomes

  1. Cambridge Cognition's Paired Associates Learning Test

    Time frame: Baseline to 6 months

    Total errors score (adjusted) - number of errors made by the participant (range: 0 to ~120). Higher scores indicate poor performance.

  2. Cambridge Neuropsychological Test Automated Battery (CANTAB)

    Time frame: Baseline to 6 months

    Composite score (higher score indicate better outcome)

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

    Time frame: Baseline to 6 months

    Total score (range 0 to 70); higher scores indicate poor performance.

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

    Time frame: Baseline to 6 months

    iADL subscore (range 0-56): Lower score indicates greater severity

  5. Safety and tolerability

    Time frame: Baseline to 6 months

    Frequency of adverse events and serious adverse events

Other outcomes

  1. Other regional brain volumes

    Time frame: Baseline to 6 and 9 months

    Change in regional brain volumes (mm3)

  2. Diffusion tensor imaging (DTI)

    Time frame: Baseline to 6 and 9 months

    Change in white matter tract diffusion (scalar values and/or mm2/sec)

  3. Resting state functional MRI

    Time frame: Baseline to 6 and 9 months

    Change in functional connectivity (z transformed correlations)

  4. Arterial spin labeling (ASL)

    Time frame: Baseline to 6 and 9 months

    Change in regional cerebral blood flow (mL/100g)

  5. Exploratory blood based biomarkers

    Time frame: Baseline to 6 and 9 months

    Change from baseline in biomarkers of AD pathology, neurogenesis and inflammation

  6. Clinical Dementia Rating (CDR)

    Time frame: Baseline to 6 and 9 months

    Sum of boxes score (CDR-SB): range 0-18

  7. Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) 14

    Time frame: Baseline to 6 and 9 months

    Total score (range 0-90)

  8. Mini Mental State Examination (MMSE)

    Time frame: Baseline to 6 and 9 months

    Total score (range 0-30)

  9. Neuropsychiatric Inventory-Questionnaire (NPI-Q)

    Time frame: Baseline to 6 and 9 months

    Total score (range 0-36). Higher scores indicate greater symptom severity

  10. EuroQol 5-Dimension / 5-Level health-related quality of life scale scores (EQ-5D-5L)

    Time frame: Baseline to 6 and 9 months

    Reported as frequency, percentage and index value.

  11. Quality of Life in Alzheimer's Disease scale (QoL-AD)

    Time frame: Baseline to 6 and 9 months

    Total score (range 13-52). Higher score indicate better QoL

  12. Zarit Burden Interview (ZBI)

    Time frame: Baseline to 6 and 9 months

    Total score (range 0-48). Higher scores indicate high burden

Sponsors and collaborators

Lead sponsor

University of Arizona

Other

Collaborators

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

Registry information

Official study 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

Acronym: REGEN-BRAIN©

Important dates

Study start
2023
Primary completion
2026
Study completion
2027
First posted
Apr 9, 2021
Registry last updated
Jun 30, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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