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

University of Southern California

Status and phase: Completed; Phase 1

Conditions: Alzheimer Disease; Mild Cognitive Impairment

Treatments: Drug: Allopregnanolone injection (intravenous solution); Drug: Placebo injection (intravenous solution)

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT02221622

1UF1AG046148 (U.S. NIH Grant/Contract)

AlloPhase1

Details and patient eligibility

About

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.

Full 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.

Enrollment: 24 patients

Sex: All

Ages: 55+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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24 participants in 4 patient groups, including a placebo group

Allopregnanolone 2 mg

Experimental group

Description:

Drug: Allopregnanolone injection (intravenous solution) once per week for 12 weeks

Treatment:

Drug: Allopregnanolone injection (intravenous solution)

Allopregnanolone 4 mg

Experimental group

Description:

Drug: Allopregnanolone injection (intravenous solution) once per week for 12 weeks

Treatment:

Drug: Allopregnanolone injection (intravenous solution)

Allopregnanolone 6-18 mg

Experimental group

Description:

Drug: Allopregnanolone injection (intravenous solution) once per week for 12 weeks

Treatment:

Drug: Allopregnanolone injection (intravenous solution)

Placebo

Placebo Comparator group

Description:

Drug: Placebo injection (intravenous solution) once per week for 12 weeks

Treatment:

Drug: Placebo injection (intravenous solution)