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

July 2, 2019 updated by: University of Southern California

Allopregnanolone Regenerative Therapeutic for MCI/AD: Dose Finding Phase 1

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

24

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90033
        • University of Southern California - Alzheimer Disease Research Center - Healthcare Consultation Center II

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

55 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Allopregnanolone 2 mg
Drug: Allopregnanolone injection (intravenous solution) once per week for 12 weeks
Drug: Allopregnanolone injection (intravenous solution)
Allopregnanolone intravenous infusion
Other Names:
  • 3α,5α-tetrahydroprogesterone
  • 3α-hydroxy-5α-pregnan-20-one
EXPERIMENTAL: Allopregnanolone 4 mg
Drug: Allopregnanolone injection (intravenous solution) once per week for 12 weeks
Drug: Allopregnanolone injection (intravenous solution)
Allopregnanolone intravenous infusion
Other Names:
  • 3α,5α-tetrahydroprogesterone
  • 3α-hydroxy-5α-pregnan-20-one
EXPERIMENTAL: Allopregnanolone 6-18 mg
Drug: Allopregnanolone injection (intravenous solution) once per week for 12 weeks
Drug: Allopregnanolone injection (intravenous solution)
Allopregnanolone intravenous infusion
Other Names:
  • 3α,5α-tetrahydroprogesterone
  • 3α-hydroxy-5α-pregnan-20-one
PLACEBO_COMPARATOR: Placebo
Drug: Placebo injection (intravenous solution) once per week for 12 weeks
Drug: Placebo injection (intravenous solution)
Placebo intravenous infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety profile: Adverse events
Time Frame: From Baseline to week 16
Incidence and severity of treatment emergent adverse events assessed weekly per treatment arm.
From Baseline to week 16
Safety profile: Clinical laboratory measurements
Time Frame: From Baseline to week 13

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
From Baseline to week 13
Safety profile: ARIA
Time Frame: From Baseline to week 13
MRI based assessment of amyloid related imaging abnormalities (ARIA); proportion of subjects with ARIA
From Baseline to week 13
Safety profile: Physical and neurological examination
Time Frame: From Baseline to week 16
To evaluate the proportion of abnormal examination findings of subjects in each treatment arm.
From Baseline to week 16
Tolerability - Maximum tolerated dose (MTD)
Time Frame: From Baseline to week 12
Onset of sedation will define the upper most limit of drug dose
From Baseline to week 12

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pharmacokinetic profile after single and multiple doses: Maximum Concentration (Cmax)
Time Frame: Weeks: 1 and 12
Measurement of maximum concentration
Weeks: 1 and 12
Pharmacokinetic profile after single and multiple doses: time attain to Cmax (Tmax)
Time Frame: Weeks: 1 and 12
Time to attain maximum concentration.
Weeks: 1 and 12
Pharmacokinetic profile after single and multiple doses: Area under the curve (AUC)
Time Frame: Weeks: 1 and 12
Pharmacokinetic parameter.
Weeks: 1 and 12
Pharmacokinetic profile after single and multiple doses: Drug Clearance (CL)
Time Frame: Weeks: 1 and 12
Pharmacokinetic parameter.
Weeks: 1 and 12
Pharmacokinetic profile after single and multiple doses: apparent volume of distribution at steady state (Vss)
Time Frame: Weeks: 1 and 12
Pharmacokinetic parameter.
Weeks: 1 and 12
Cognitive tests (ADAS-Cog; MMSE/MoCA; ADCS-CGIC; CogState)
Time Frame: Baseline to Week 13
Alzheimer's disease Assessment Scale Cognitive Subscale 14 (ADAS-Cog); Mini-Mental State Exam (MMSE); Montreal Cognitive Assessment (MoCA); Alzheimer's disease Cooperative Study Clinical Global Impression of Change (ADCS-CGIC); CogState 12-min battery (CogState)
Baseline to Week 13
Brain MRI volumetrics
Time Frame: Baseline and Week 13
Gray matter, white matter and hippocampal volume measurements, including subfield analysis.
Baseline and Week 13

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Southern California

Collaborators

National Institute on Aging (NIA)

Investigators

  • Principal Investigator: Roberta D Brinton, Ph.D., University of Southern California
  • Principal Investigator: Lon S Schneider, M.D., University of Southern California

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2014

Primary Completion (ACTUAL)

February 1, 2018

Study Completion (ACTUAL)

February 1, 2018

Study Registration Dates

First Submitted

July 2, 2014

First Submitted That Met QC Criteria

August 18, 2014

First Posted (ESTIMATE)

August 20, 2014

Study Record Updates

Last Update Posted (ACTUAL)

July 5, 2019

Last Update Submitted That Met QC Criteria

July 2, 2019

Last Verified

May 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AlloPhase1
  • 1UF1AG046148 (NIH)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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