Allopregnanolone for Mild Cognitive Impairment Due to Alzheimer's Disease or Mild AD

University of Southern California24 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Mild Cognitive Impairment Alzheimer Disease

Interventions

Allopregnanolone injection (intravenous solution)DRUG

Allopregnanolone intravenous infusion

Placebo injection (intravenous solution)DRUG

Placebo intravenous infusion

Eligibility

Sex: ALLMin age: 55 Years

Medical Language ↔ Plain English

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

Locations (1)

University of Southern California - Alzheimer Disease Research Center - Healthcare Consultation Center II

Los Angeles, California, United States

Outcomes

Primary Outcomes

Safety profile: Adverse events

Incidence and severity of treatment emergent adverse events assessed weekly per treatment arm.

Time frame: From Baseline to week 16

Safety profile: Clinical laboratory measurements

Evaluating the proportion of subjects exceeding pre-established critical values per treatment arm: Alanine aminotransferase (ALT, U/L) \> 5 times upper normal limit Aspartate aminotransferase (AST, U/L) \> 5 times upper normal limit Total serum bilirubin (mg/dl) \> 2 times upper normal limit Serum creatinine (mg/dl) \> 2 times upper normal limit Serum creatine phosphokinase (U/L) \> 5 times upper normal limit

Time frame: From Baseline to week 13

Safety profile: ARIA

MRI based assessment of amyloid related imaging abnormalities (ARIA); proportion of subjects with ARIA

Time frame: From Baseline to week 13

Safety profile: Physical and neurological examination

To evaluate the proportion of abnormal examination findings of subjects in each treatment arm.

Time frame: From Baseline to week 16

Tolerability - Maximum tolerated dose (MTD)

Onset of sedation will define the upper most limit of drug dose

Time frame: From Baseline to week 12

Secondary Outcomes

Pharmacokinetic profile after single and multiple doses: Maximum Concentration (Cmax)

Measurement of maximum concentration

Time frame: Weeks: 1 and 12

Pharmacokinetic profile after single and multiple doses: time attain to Cmax (Tmax)

Data from ClinicalTrials.gov

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