This site became the new ClinicalTrials.gov on June 19th. Learn more.
Show more
ClinicalTrials.gov Menu IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu IMPORTANT: Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu
Give us feedback

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

This study is currently recruiting participants.
See Contacts and Locations
Verified April 2017 by Roberta Brinton, University of Southern California
Sponsor:
Collaborator:
National Institute on Aging (NIA)
Information provided by (Responsible Party):
Roberta Brinton, University of Southern California
ClinicalTrials.gov Identifier:
NCT02221622
First received: July 2, 2014
Last updated: April 18, 2017
Last verified: April 2017
  Purpose
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.

Condition Intervention Phase
Mild Cognitive Impairment Alzheimer Disease Drug: Allopregnanolone injection (intravenous solution) Drug: Placebo injection (intravenous solution) Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Allopregnanolone Regenerative Therapeutic for MCI/AD: Dose Finding Phase 1

Resource links provided by NLM:


Further study details as provided by Roberta Brinton, University of Southern California:

Primary Outcome Measures:
  • Safety and tolerability as measured by vital signs, clinical laboratory measurements, adverse events, brain MRI, clinical assessment and examination. [ Time Frame: From Baseline to Week 16 ]

Secondary Outcome Measures:
  • Pharmacokinetic profile after single and multiple doses: Maximum Concentration (Cmax) [ Time Frame: Weeks: 1 and 12 ]
  • Pharmacokinetic profile after single and multiple doses: time attain to Cmax (Tmax) [ Time Frame: Weeks: 1 and 12 ]
  • Pharmacokinetic profile after single and multiple doses: Area under the curve (AUC) [ Time Frame: Weeks: 1 and 12 ]
  • Pharmacokinetic profile after single and multiple doses: Drug Clearance (CL) [ Time Frame: 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 ]
  • 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)

  • Structural and functional brain MRI [ Time Frame: Baseline and Week 13 ]

Estimated Enrollment: 24
Study Start Date: August 2014
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: November 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

Ages Eligible for Study:   55 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02221622

Contacts
Contact: Gerson Hernandez (323) 865-ALLO (323) 865-2556 gersonhe@usc.edu
Contact: Gerson Hernandez (323) 442-7608 gersonhe@usc.edu

Locations
United States, California
University of Southern California - Alzheimer Disease Research Center - Healthcare Consultation Center II Recruiting
Los Angeles, California, United States, 90033
Sponsors and Collaborators
University of Southern California
National Institute on Aging (NIA)
Investigators
Principal Investigator: Roberta Diaz Brinton, Ph.D. University of Southern California
Principal Investigator: Lon S. Schneider, M.D. University of Southern California
  More Information

Responsible Party: Roberta Brinton, Professor, University of Southern California
ClinicalTrials.gov Identifier: NCT02221622     History of Changes
Other Study ID Numbers: AlloPhase1
1UF1AG046148 ( U.S. NIH Grant/Contract )
Study First Received: July 2, 2014
Last Updated: April 18, 2017

Keywords provided by Roberta Brinton, University of Southern California:
Alzheimer's disease
Mild Cognitive Impairment
Dementia
Regenerative therapeutic

Additional relevant MeSH terms:
Alzheimer Disease
Cognition Disorders
Mild Cognitive Impairment
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Pharmaceutical Solutions
Pregnanolone
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 21, 2017