Alzheimer Dementia, Late Onset Alzheimer Disease, Neurodegenerative Diseases
Conditions
Keywords
Mild Alzheimer Disease, Regenerative Therapeutic, Neurogenesis, Allopregnanolone
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.
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.
Interventions
DRUGAllopregnanolone
Allopregnanolone 4mg IV via 30-minute infusion, once per week.
OTHERPlacebo
Normal saline solution IV via 30-minute infusion, once per week
Sponsors
University of Arizona
National Institute on Aging (NIA)
Syneos Health
University of Southern California
ADM Diagnostics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
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.
Intervention model description
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).
Eligibility
Sex/Gender
ALL
Age
55 Years to 80 Years
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hippocampal volume | Baseline to 6 months | mm3 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cambridge Cognition's Paired Associates Learning Test | Baseline to 6 months | Total errors score (adjusted) - number of errors made by the participant (range: 0 to \~120). Higher scores indicate poor performance. |
| Cambridge Neuropsychological Test Automated Battery (CANTAB) | Baseline to 6 months | Composite score (higher score indicate better outcome) |
| Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) 11 | Baseline to 6 months | Total score (range 0 to 70); higher scores indicate poor performance. |
| Alzheimer's Disease Cooperative Study (ADCS) Instrumental Activities of Daily (iADL) Living (iADL) | Baseline to 6 months | iADL subscore (range 0-56): Lower score indicates greater severity |
| Safety and tolerability | Baseline to 6 months | Frequency of adverse events and serious adverse events |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORRoberta D Brinton, PhD
University of Arizona
PRINCIPAL_INVESTIGATORLon Schneider, MD
University of Southern California
STUDY_DIRECTORGerson D Hernandez, MD, MPH
University of Arizona
Outcome results
None listed