Clinical trial NCT05227820: Insulin-Sensitizing Anti-Inflammatory Small Molecule for Investigative Treatment of Dementia
Official title: Anti-Inflammatory, Insulin-Sensitizing Agent for Treatment of Cognitive Decline Due to Degenerative Dementias
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Alzheimer Disease
Lead sponsor: Neurological Associates of West Los Angeles
Sponsor class: OTHER
Collaborators: name: BioVie Inc.
First posted: 2022-02-07
Enrollment: 23
Sex: ALL
Minimum age (years): 55
Maximum age (years): 89
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study seeks to measure changes in cognition through verbal and visual test procedures and changes in biomarkers of Alzheimer's disease and inflammatory and metabolic parameters that can be measure in the central nervous system (CNS) with advanced neuroimaging techniques in patients treated with NE3107 (17a-ethynyl-androst-5-3b,7b,17b-triol).

Detailed description: Considering how many people are in a state of mild cognitive impairment (MCI) and frank dementia, there is a substantial cost to society in terms of financial burden and suffering. Degenerative conditions that result in cognitive change in middle and late life are frequently associated with abnormal deposits of protein material (e.g., amyloid, phospho-tau) which interfere with neuronal function and viability. Inflammation and insulin resistance in the CNS and abnormal protein deposition and resultant physiological impairment characterize conditions of the Alzheimer's dementia (AD) type.

Neuroinflammation prompts AD progression, impaired cholesterol efflux and reduced insulin signaling (insulin resistance). Insulin resistance has been considered a risk factor as well as a feature of AD, and has also been associated with increased aß-42 secretion, neuritic plaque burden, abnormal insulin receptor performance, decreased glucose metabolism, and consequently decreased cognitive performance.

No therapy exists that has been proven to halt or reverse the progressive deposition of abnormal proteins or the attendant neurophysiological deterioration. Various investigational therapies aim to target the pathophysiological processes of AD; from combating abnormal protein deposition, to targeting sources of systemic and neuroinflammation, to providing cholinergic, hormonal, and metabolic support. A promising area of research is the ongoing use of insulin synthesizers as a therapeutic option for AD.

Several Phase 3 studies have been initiated and/or completed with compounds such as Semaglutide, a hormone that stimulates insulin signaling, Metformin, an insulin synthesizer, and NE3107, an anti-inflammatory insulin-sensitizing agent.

This study seeks to measure changes in cognition through verbal and visual test procedures and changes in biomarkers of Alzheimer's disease and inflammatory and metabolic parameters that can be measured in the CNS with advanced neuroimaging techniques in patients treated with NE3107 (17a-ethynyl-androst-5-ene-3b,7b,17b-triol).

Investigational Product

The drug under investigation is NE3107 (17a-ethynyl-androst-5-ene-3b,7b,17b-triol). NE3107 is formulated with common excipients used in oral medications in #2 hard gelatin capsules. The capsules are designed for oral administration. NE3107 capsules are stable at room temperature for at least 18 months. Stability of the capsules used in this study will be monitored by a concurrent stability study conducted by the capsule manufacturer and the holder of the primary IND, Biovie, Inc (Santa Monica, CA).

Eligibility criteria: In order for a subject to be considered for this study, the following criterion is required:

Inclusion Criteria:

* Cognitive decline with Clinical Dementia Rating (CDR) score of 0.5 to 1, suggesting mild cognitive impairment to mild dementia.
* Participants must be between the ages of 50-89
* Primary cognitive complaint must be memory Impairment without movement or psychiatric explanation/diagnosis
* Participants must show at least one abnormal imaging biomarker and none of the exclusion criteria below.

Exclusion Criteria:

In order for a subject to be considered for this study, he/she may NOT have any of the following:

* Subjects with contraindications for lumbar puncture, such as bleeding abnormalities, use of anticoagulant medications, and local skin or spine abnormalities
* Reversible causes of cognitive impairment that explains the clinical status entirely, such as hypothyroidism, depression
* Advanced stages of any terminal illness or any active cancer that requires chemotherapy
* History of breast cancer
* Women with child-bearing potential who are not willing to use a double-barrier birth control method
* Males not willing to use a double-barrier birth control method with female sex partners with child-bearing potential

Primary outcomes:
measure: Change in fMRI
timeFrame: 3 Months
Secondary outcomes:
measure: Clinical Dementia Rating Change as Calculated From the Quick Dementia Rating Scale Change
timeFrame: 3 Months
measure: Montreal Cognitive Assessment (MoCA) Change
timeFrame: 3 Months
measure: Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) Change
timeFrame: 3 Months
measure: Mini-Mental State Examination (MMSE) Change
timeFrame: 3 Months
Other outcomes:
Locations:
city: Santa Monica
country: United States
facility: Neurological Associates - The Interventional Group
state: California
Study officials:
affiliation: Neurological Associates The Interventional Group/The Regenesis Project
name: Sheldon Jordan
role: PRINCIPAL_INVESTIGATOR
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