Alzheimer Disease
Conditions
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).
Interventions
DRUGNE3107
Participants will take 20mg twice daily (BID) approximately 12 hours apart. The dose will be stable the duration of the study intervention (3 months)
Sponsors
BioVie Inc.
Neurological Associates of West Los Angeles
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
55 Years to 89 Years
Healthy volunteers
No
Inclusion 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in fMRI | 3 Months | Primary endpoints assessed changes from baseline in neurophysiological health and oxidative stress using advanced neuroimaging analyses. Analysis methods utilized blinded expert evaluation between baseline and completion scans. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Dementia Rating Change as Calculated From the Quick Dementia Rating Scale Change | 3 Months | Quick Dementia Rating Scale (QDRS) The Quick Dementia Rating Scale (QDRS) is an interview-based tool administered by study officials to participants' caregivers used to obtain observations from a consistent source. The QDRS form consists of 10 categorical questions (5 cognitive, 5 functional), each with 5 detailed options depicting the level of impairment as either 0 (normal), 0.5 (mild/inconsistent impairment), 1 (mild/consistent impairment), 2 (moderate impairment), or 3 (severe impairment). Based on the conversion table outlined in Dr. James Galvin's research (2015), total QDRS scores were converted to Clinical Dementia Rating (CDR) scale levels ranging from 0 (normal aging), 0.5 (mild cognitive impairment), 1 (mild dementia), 2 (moderate dementia), and 3 (severe dementia). |
| Montreal Cognitive Assessment (MoCA) Change | 3 Months | The MoCA evaluates frontal-executive functions (e.g., verbal abstraction and mental calculation), language (e.g., confrontation naming, phonemic fluency), orientation (e.g., person, place, date, day of the week, and time), visuospatial construction (e.g., simple figure copy), divided visual attention, and immediate and delayed memory of unstructured information. MoCA scores range from 0-30 possible points; 26 or greater is considered to reflect normal cognitive status. |
| Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) Change | 3 Months | The ADAS-Cog evaluates participants' cognitive ability. It is composed of 11 parts that measure word recall, object/figure naming, command following, constructional praxis, ideational praxis, orientation, word recognition, test direction recall, spoken language, comprehension, and word-finding difficulty. The ADAS-Cog is scored from 0-70 by measuring the errors made in each task, with a score of 70 representing the most severe impairment. A point reduction of 3.1 to 3.8 has been found to be the minimal clinically important difference (Schrag & Schott, 2012). A change will be evaluated from baseline to completion. |
| Mini-Mental State Examination (MMSE) Change | 3 Months | The MMSE is a 30-point questionnaire that evaluates cognition. The MMSE includes specific tasks that assess orientation, attention, memory, language, and visual-spatial skills. MMSE scores range from 0 - 30 possible points; 0-17: severe cognitive impairment, 18-23: mild cognitive impairment, 24-30: no cognitive impairment. A point decrease \>/= to 3 on the MMSE has been identified as the minimally clinically important difference (Andres, 2019). A change will be evaluated from baseline to completion. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Experimental Arm: NE3107 All participants will take 20mg BID (12 hours apart) of NE3107 for 3 months.
NE3107: Participants will take 20mg twice daily (BID) approximately 12 hours apart. The dose will be stable the duration of the study intervention (3 months) | 23 |
| Total | 23 |
Baseline characteristics
| Characteristic | Experimental Arm: NE3107 |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 18 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants |
| Age, Continuous | 71 years STANDARD_DEVIATION 2.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 23 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 23 Participants |
| Region of Enrollment United States | 23 participants |
| Sex: Female, Male Female | 16 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 23 |
| other Total, other adverse events | 8 / 23 |
| serious Total, serious adverse events | 0 / 23 |
Outcome results
Primary
Change in fMRI
Primary endpoints assessed changes from baseline in neurophysiological health and oxidative stress using advanced neuroimaging analyses. Analysis methods utilized blinded expert evaluation between baseline and completion scans.
Time frame: 3 Months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Experimental Arm: NE3107 | Change in fMRI | 11 Participants |
Secondary
Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) Change
The ADAS-Cog evaluates participants' cognitive ability. It is composed of 11 parts that measure word recall, object/figure naming, command following, constructional praxis, ideational praxis, orientation, word recognition, test direction recall, spoken language, comprehension, and word-finding difficulty. The ADAS-Cog is scored from 0-70 by measuring the errors made in each task, with a score of 70 representing the most severe impairment. A point reduction of 3.1 to 3.8 has been found to be the minimal clinically important difference (Schrag & Schott, 2012). A change will be evaluated from baseline to completion.
Time frame: 3 Months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Experimental Arm: NE3107 | Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) Change | 13 Participants |
Secondary
Clinical Dementia Rating Change as Calculated From the Quick Dementia Rating Scale Change
Quick Dementia Rating Scale (QDRS) The Quick Dementia Rating Scale (QDRS) is an interview-based tool administered by study officials to participants' caregivers used to obtain observations from a consistent source. The QDRS form consists of 10 categorical questions (5 cognitive, 5 functional), each with 5 detailed options depicting the level of impairment as either 0 (normal), 0.5 (mild/inconsistent impairment), 1 (mild/consistent impairment), 2 (moderate impairment), or 3 (severe impairment). Based on the conversion table outlined in Dr. James Galvin's research (2015), total QDRS scores were converted to Clinical Dementia Rating (CDR) scale levels ranging from 0 (normal aging), 0.5 (mild cognitive impairment), 1 (mild dementia), 2 (moderate dementia), and 3 (severe dementia).
Time frame: 3 Months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Experimental Arm: NE3107 | Clinical Dementia Rating Change as Calculated From the Quick Dementia Rating Scale Change | 14 Participants |
Secondary
Mini-Mental State Examination (MMSE) Change
The MMSE is a 30-point questionnaire that evaluates cognition. The MMSE includes specific tasks that assess orientation, attention, memory, language, and visual-spatial skills. MMSE scores range from 0 - 30 possible points; 0-17: severe cognitive impairment, 18-23: mild cognitive impairment, 24-30: no cognitive impairment. A point decrease \>/= to 3 on the MMSE has been identified as the minimally clinically important difference (Andres, 2019). A change will be evaluated from baseline to completion.
Time frame: 3 Months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Experimental Arm: NE3107 | Mini-Mental State Examination (MMSE) Change | 8 Participants |
Secondary
Montreal Cognitive Assessment (MoCA) Change
The MoCA evaluates frontal-executive functions (e.g., verbal abstraction and mental calculation), language (e.g., confrontation naming, phonemic fluency), orientation (e.g., person, place, date, day of the week, and time), visuospatial construction (e.g., simple figure copy), divided visual attention, and immediate and delayed memory of unstructured information. MoCA scores range from 0-30 possible points; 26 or greater is considered to reflect normal cognitive status.
Time frame: 3 Months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Experimental Arm: NE3107 | Montreal Cognitive Assessment (MoCA) Change | 9 Participants |