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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02221622
Recruitment Status : Completed
First Posted : August 20, 2014
Last Update Posted : July 5, 2019
Sponsor:
Collaborator:
National Institute on Aging (NIA)
Information provided by (Responsible Party):
University of Southern California

Tracking Information
First Submitted Date  ICMJE July 2, 2014
First Posted Date  ICMJE August 20, 2014
Last Update Posted Date July 5, 2019
Study Start Date  ICMJE August 2014
Actual Primary Completion Date February 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 31, 2018)
  • Safety profile: Adverse events [ Time Frame: From Baseline to week 16 ]
    Incidence and severity of treatment emergent adverse events assessed weekly per treatment arm.
  • 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
  • Safety profile: ARIA [ Time Frame: From Baseline to week 13 ]
    MRI based assessment of amyloid related imaging abnormalities (ARIA); proportion of subjects with ARIA
  • 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.
  • Tolerability - Maximum tolerated dose (MTD) [ Time Frame: From Baseline to week 12 ]
    Onset of sedation will define the upper most limit of drug dose
Original Primary Outcome Measures  ICMJE
 (submitted: August 18, 2014)
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 ]
Change History Complete list of historical versions of study NCT02221622 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 31, 2018)
  • Pharmacokinetic profile after single and multiple doses: Maximum Concentration (Cmax) [ Time Frame: Weeks: 1 and 12 ]
    Measurement of maximum concentration
  • Pharmacokinetic profile after single and multiple doses: time attain to Cmax (Tmax) [ Time Frame: Weeks: 1 and 12 ]
    Time to attain maximum concentration.
  • Pharmacokinetic profile after single and multiple doses: Area under the curve (AUC) [ Time Frame: Weeks: 1 and 12 ]
    Pharmacokinetic parameter.
  • Pharmacokinetic profile after single and multiple doses: Drug Clearance (CL) [ Time Frame: Weeks: 1 and 12 ]
    Pharmacokinetic parameter.
  • Pharmacokinetic profile after single and multiple doses: apparent volume of distribution at steady state (Vss) [ Time Frame: Weeks: 1 and 12 ]
    Pharmacokinetic parameter.
  • 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)
  • Brain MRI volumetrics [ Time Frame: Baseline and Week 13 ]
    Gray matter, white matter and hippocampal volume measurements, including subfield analysis.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 18, 2014)
  • 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 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Allopregnanolone for Mild Cognitive Impairment Due to Alzheimer's Disease or Mild AD
Official Title  ICMJE Allopregnanolone Regenerative Therapeutic for MCI/AD: Dose Finding Phase 1
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Mild Cognitive Impairment
  • Alzheimer Disease
Intervention  ICMJE
  • Drug: Allopregnanolone injection (intravenous solution)
    Allopregnanolone intravenous infusion
    Other Names:
    • 3α,5α-tetrahydroprogesterone
    • 3α-hydroxy-5α-pregnan-20-one
  • Drug: Placebo injection (intravenous solution)
    Placebo intravenous infusion
Study Arms  ICMJE
  • Experimental: Allopregnanolone 2 mg
    Drug: Allopregnanolone injection (intravenous solution) once per week for 12 weeks
    Intervention: Drug: Allopregnanolone injection (intravenous solution)
  • Experimental: Allopregnanolone 4 mg
    Drug: Allopregnanolone injection (intravenous solution) once per week for 12 weeks
    Intervention: Drug: Allopregnanolone injection (intravenous solution)
  • Experimental: Allopregnanolone 6-18 mg
    Drug: Allopregnanolone injection (intravenous solution) once per week for 12 weeks
    Intervention: Drug: Allopregnanolone injection (intravenous solution)
  • Placebo Comparator: Placebo
    Drug: Placebo injection (intravenous solution) once per week for 12 weeks
    Intervention: Drug: Placebo injection (intravenous solution)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 26, 2015)
24
Original Estimated Enrollment  ICMJE
 (submitted: August 18, 2014)
32
Actual Study Completion Date  ICMJE February 2018
Actual Primary Completion Date February 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 55 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02221622
Other Study ID Numbers  ICMJE AlloPhase1
1UF1AG046148 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of Southern California
Study Sponsor  ICMJE University of Southern California
Collaborators  ICMJE National Institute on Aging (NIA)
Investigators  ICMJE
Principal Investigator: Roberta D Brinton, Ph.D. University of Southern California
Principal Investigator: Lon S Schneider, M.D. University of Southern California
PRS Account University of Southern California
Verification Date May 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP