Clinical trial NCT02221622: Allopregnanolone for Mild Cognitive Impairment Due to Alzheimer's Disease or Mild AD
Official title: Allopregnanolone Regenerative Therapeutic for MCI/AD: Dose Finding Phase 1
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Mild Cognitive Impairment
Alzheimer Disease
Keywords: Alzheimer's disease
Mild Cognitive Impairment
Dementia
Regenerative therapeutic
Lead sponsor: University of Southern California
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
First posted: 2014-08-20
Enrollment: 24
Sex: ALL
Minimum age (years): 55
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the safety and tolerability of allopregnanolone, a naturally occurring brain steroid, in mild cognitive impairment and early Alzheimer's disease participants. The primary goal is to determine the maximally tolerated dose.

Detailed description: 1) Each dose group will be comprised of 8 participants (6 randomized to allopregnanolone; 2 randomized to placebo) administered one dose of allopregnanolone or placebo once per week for 12 weeks. A higher dose will be administered to the next group of participants when the lower dose is shown to be safe and tolerable. 2) Pharmacokinetic analyses will be conducted on blood samples taken from participants at the beginning and end of the trial. 3) The trial will assess safety including via MRI brain imaging.

Eligibility criteria: Inclusion Criteria:

* Men or postmenopausal women
* 55 years of age or older
* Diagnosis of MCI due to AD or mild AD
* MMSE \> 20 at screen
* Capacity to provide informed consent
* Residing in the community with a caregiver able to accompany the patient to clinic visits
* No medical contraindications to participation
* Willingness to comply with study procedures

Exclusion Criteria:

* Use of benzodiazepines, sedative/hypnotics, anticonvulsants, antipsychotics, and other drugs that might interact with the GABA-A receptor complex
* Seizure disorder, history of stroke, focal brain lesion, traumatic brain injury, substance abuse, malignancy
* Clinically significant laboratory or ECG abnormality
* MRI indicative of any other significant abnormality, including but not limited to evidence of a cerebral contusion, encephalomalacia, aneurysms, vascular malformations, subdural hematoma, or space occupying lesions
* Any condition that would contraindicate an MRI such as the presence of metallic objects in the eyes, skin, heart, or body

Primary outcomes:
measure: Safety profile: Adverse events
timeFrame: From Baseline to week 16
measure: Safety profile: Clinical laboratory measurements
timeFrame: From Baseline to week 13
measure: Safety profile: ARIA
timeFrame: From Baseline to week 13
measure: Safety profile: Physical and neurological examination
timeFrame: From Baseline to week 16
measure: Tolerability - Maximum tolerated dose (MTD)
timeFrame: From Baseline to week 12
Secondary outcomes:
measure: Pharmacokinetic profile after single and multiple doses: Maximum Concentration (Cmax)
timeFrame: Weeks: 1 and 12
measure: Pharmacokinetic profile after single and multiple doses: time attain to Cmax (Tmax)
timeFrame: Weeks: 1 and 12
measure: Pharmacokinetic profile after single and multiple doses: Area under the curve (AUC)
timeFrame: Weeks: 1 and 12
measure: Pharmacokinetic profile after single and multiple doses: Drug Clearance (CL)
timeFrame: Weeks: 1 and 12
measure: Pharmacokinetic profile after single and multiple doses: apparent volume of distribution at steady state (Vss)
timeFrame: Weeks: 1 and 12
measure: Cognitive tests (ADAS-Cog; MMSE/MoCA; ADCS-CGIC; CogState)
timeFrame: Baseline to Week 13
measure: Brain MRI volumetrics
timeFrame: Baseline and Week 13
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of Southern California - Alzheimer Disease Research Center - Healthcare Consultation Center II
state: California
Study officials:
affiliation: University of Southern California
name: Roberta D Brinton, Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Southern California
name: Lon S Schneider, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.