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

Alzheimer Disease Clinical Trial

— Allo  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02221622
• Other study ID #: AlloPhase1
• Secondary ID: 1UF1AG046148
• Status: Completed
• Phase: Phase 1
• Start date: August 2014
• Est. completion date: February 2018

Study information

• Verified date: May 2018
• Source: University of Southern California
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: February 2018
• Est. primary completion date: February 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 55 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Alzheimer Disease
• Cognitive Dysfunction
• Mild Cognitive Impairment

Intervention

Drug:
• Allopregnanolone injection (intravenous solution)
Allopregnanolone intravenous infusion
• Placebo injection (intravenous solution)
Placebo intravenous infusion

Locations

Country	Name	City	State
United States	University of Southern California - Alzheimer Disease Research Center - Healthcare Consultation Center II	Los Angeles	California

Sponsors (2)

Lead Sponsor	Collaborator
University of Southern California	National Institute on Aging (NIA)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety profile: Adverse events	Incidence and severity of treatment emergent adverse events assessed weekly per treatment arm.	From Baseline to week 16
Primary	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	From Baseline to week 13
Primary	Safety profile: ARIA	MRI based assessment of amyloid related imaging abnormalities (ARIA); proportion of subjects with ARIA	From Baseline to week 13
Primary	Safety profile: Physical and neurological examination	To evaluate the proportion of abnormal examination findings of subjects in each treatment arm.	From Baseline to week 16
Primary	Tolerability - Maximum tolerated dose (MTD)	Onset of sedation will define the upper most limit of drug dose	From Baseline to week 12
Secondary	Pharmacokinetic profile after single and multiple doses: Maximum Concentration (Cmax)	Measurement of maximum concentration	Weeks: 1 and 12
Secondary	Pharmacokinetic profile after single and multiple doses: time attain to Cmax (Tmax)	Time to attain maximum concentration.	Weeks: 1 and 12
Secondary	Pharmacokinetic profile after single and multiple doses: Area under the curve (AUC)	Pharmacokinetic parameter.	Weeks: 1 and 12
Secondary	Pharmacokinetic profile after single and multiple doses: Drug Clearance (CL)	Pharmacokinetic parameter.	Weeks: 1 and 12
Secondary	Pharmacokinetic profile after single and multiple doses: apparent volume of distribution at steady state (Vss)	Pharmacokinetic parameter.	Weeks: 1 and 12
Secondary	Cognitive tests (ADAS-Cog; MMSE/MoCA; ADCS-CGIC; CogState)	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
Secondary	Brain MRI volumetrics	Gray matter, white matter and hippocampal volume measurements, including subfield analysis.	Baseline and Week 13