Phase II Open Label Study for the Use of Insulin-Sensitizer for Treatment of Cognitive Decline

• Status: Not yet recruiting
• Trial end date: 2022-05-01
• Target enrollment: 0
• Participant gender: All

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).

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Neurological Associates of West Los Angeles
• Collaborator: BioVie Inc.

Criteria

Inclusion Criteria:

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

Cognitive decline with Clinical Dementia Rating (CDR) score of 0.5 to 1, suggesting mild cognitive impairment to mild dementia.

The QDRS scale will be given to all patients; a cutoff range for QDRS scores has been specified as 1.5-17.5 to qualify patients with a clinical dementia score (CDR) of 0.5 to 2.

All patients will have a lumbar puncture for Aß42 and Tau proteins for Alzheimer's Spectrum. This spinal fluid examination has been shown to be both sensitive and specific for Alzheimer's disease. Cerebrospinal fluid (CSF) tau levels are also elevated in alpha synucleinopathy and frontotemporal lobar degeneration. The lumbar puncture is performed at entry. The physician may also request it be repeated at 3 months.

All patients will have an advanced MRI of the brain to include volume measurement of the hippocampus, ASL perfusion scan and MRS of prefrontal, precuneus, and hippocampus. Patients with cognitive decline have decreased perfusion in temporal parietal or frontal regions of the brain with ASL perfusion, or show characteristic change in MRS or volumetric evaluation compared to age-matched control subjects. MRI will also demonstrate if patients have tumors, hydrocephalus, subdural hematomas and other structural etiologies of cognitive decline.

On entry, patients will be tested for evidence of amyloid, CDR stage of 0.5 to 2 and at least one abnormal imaging biomarker and none of the exclusion criteria below. Baseline and completion testing will include the Quick Dementia Rating System (QDRS) for staging and the following battery of tests: Mini-Mental Status Evaluation (MMSE), Alzheimer's Disease Assessment Scale - Cognitive (ADAS-COG12), Quick Dementia Rating Scale (QDRS), Multimodal MRI of the brain; acquisition to include: high resolution structural T1, T2 Flair, susceptibility weighted imaging (SWI), MRS of the precuneus, resting BOLD, ASL, Neuromelanin, DTI-NODDI, Fasting plasma glucose and insulin levels.

CSF studies have demonstrated good sensitivity and specificity for mild cognitive impairment (MCI) and dementia of the Alzheimer's type. MRI volumetrics, perfusion scans and MR spectroscopy have shown to be of excellent discriminating value among AD, Parkinson's Disease Dementia (PDD)/ Dementia with Lewy Bodies (DLB) and Frontal Temporal Lobar Degeneration (FTLD) subgroups and is responsive to change as patient's progress from MCI to dementia.

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