A Pivotal Study of Sensory Stimulation in Alzheimer's Disease (Hope Study, CA-0011)

Study Overview
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Brief Summary
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This is a randomized, double-blind, sham-controlled, adaptive-design pivotal study of sensory stimulation in subjects with mild to moderate Alzheimer's disease. Approximately 530 subjects will be randomized to 12 months of daily treatment with either Active or Sham Sensory Stimulation Systems. Efficacy will be measured using the Alzheimer's Disease Cooperative Study- Activities of Daily Living (ADCS-ADL) assessment and a combined statistical test (CST) of the ADCS-ADL and the Mini-Mental State Exam (MMSE).

Detailed Description
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This is a multicenter, randomized, double-blind, sham-controlled, adaptive design pivotal study. The objective of the study will be to assess efficacy of gamma sensory stimulation (visual and audio) in slowing disease progression versus Sham for subjects with mild to moderate AD as measured functionally by the Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) assessment and a combined statistical test (CST) for ADCS-ADL and the Mini-Mental State Exam (MMSE). Secondary objectives will include measures of cognition and neuroanatomical change. Five-hundred and thirty (530) Mild to Moderate Alzheimer's disease subjects (MMSE 15-28) will be recruited at up to 70 clinical sites in the United States and randomized in a 1:1 ratio (Treatment: Control). In the Treatment Group, subjects will be treated with the Active Sensory Stimulation System once daily. In the Control Group, subjects are treated with a Sham Sensory Stimulation System once daily. Daily treatment is planned for up to 12 months. Subjects will attend study visits for informed consent, screening and baseline, then at 3-Months, 6-Months, 9-Months (by phone), 12 Months and 13 Months (for safety follow-up). Some clinical sites will be included in a substudy evaluating additional fluid biomarkers. Select participants enrolled at these sites will undergo a lumbar puncture to collect cerebrospinal fluid (CSF) at Baseline, 3 Months, and 12 Months.

Official Title
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A Randomized, Double-blind, Sham-controlled, Adaptive- Design Pivotal Study of Sensory Stimulation in Subjects With Alzheimer's Disease (Hope Study, CA-0011)

Conditions
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MCI, Alzheimer Disease, Alzheimer Disease 1, Alzheimer Disease 2, Alzheimer Disease 3, Alzheimer Disease, Early Onset, Alzheimer Disease, Late Onset, Alzheimer Disease 9, Alzheimer Disease 4, Alzheimer Disease 7, Alzheimer Disease 17, Alzheimer's Dementia Late Onset, Alzheimer Disease 5, Alzheimer Disease 6, Alzheimer Disease 8, Alzheimer Disease 10, Alzheimer Disease 11, Alzheimer Disease 12, Alzheimer Disease 13, Alzheimer Disease 14, Alzheimer Disease 15, Alzheimer Disease 16, Alzheimer Disease 18, Alzheimer Disease 19, Dementia, Dementia Alzheimers, Dementia, Mild, Dementia of Alzheimer Type, Dementia Moderate, Dementia Senile, Mild Cognitive Impairment, Mild Dementia, Cognitive Impairment, Cognitive Decline, Cognitive Impairment, Mild

Intervention / Treatment
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* Device: Sensory Stimulation System (GS120) - Active
* Device: Sensory Stimulation System (GS120) - Sham


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and Women age 50-90 Alzheimer's disease diagnosis with at least 6-month decline in cognitive function Non-childbearing potential or using adequate birth control Mini-Mental State Exam (MMSE) 15-28 Available/consenting Study Partner Able to identify a Legally Authorized Representative (LAR) Stable chronic conditions at least 30 days Formal education of 8 or more years Adequate vision (Able to detect light) and hearing Mobility sufficient for compliance with testing procedures (ambulatory or aided-ambulatory, i.e. cane or walker) Amyloid or phosphorylated Tau positivity Exclusion Criteria: Seizure disorder Hospitalization in previous 30 days Living in continuous care nursing home (assisted living permitted) Inability to have an MRI or significant abnormality on MRI screening Geriatric Depression Scale (GDS) >6 Suicidality (current or previous 6 months) Serious neurological diseases affecting the Central Nervous System, including: other primary degenerative dementias (Lewy-body dementia, fronto-temporal dementia, Huntington's disease, Creutzfeldt-Jakob disease, Down syndrome, mixed dementia, etc), neurodegenerative conditions (Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, etc), serious infection of the brain (meningitis/encephalitis), or history of multiple concussions. Metabolic or systemic diseases affecting the central nervous system (syphilis, B12 or folate deficiency, etc) Schizophrenia or bipolar disorder Heart disease, chronic liver, kidney, or respiratory disease, or uncontrolled diabetes or thyroid disease Cancer history within previous 2 years (except resolved non-melanoma skin or stable prostate) Nootropic drugs except stable acetylcholinesterase inhibitors Drug or Alcohol abuse in previous 12 months Previous exposure to Anti-amyloid-beta vaccines Immunomodulators or passive immunotherapies for AD (ie, monoclonal antibodies) in the 6 months prior to consent or during study Exposure to BACE (β-Site amyloid precursor protein cleaving enzyme) inhibitors within the 6 months prior to consent Involved in a previous Cognito study or gamma therapy study Active treatment with Memantine (Namenda or Namzaric) within previous 30 days Life expectancy < 24 months Participants involved in the Fluid Biomarker substudy also must not have contraindications to lumbar puncture. For more information visit: https://www.hopestudyforad.com/

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, Double-blind, Sham-controlled, Adaptive-Design Pivotal Study of Sensory Stimulation in Subjects with Alzheimer's Disease
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active<br>Treatment Group: Subjects are treated with the Active Sensory Stimulation System at home for 60 minutes daily for up to12 months. | Device: Sensory Stimulation System (GS120) - Active<br>* Sensory Stimulation System (GS120) - Active settings<br>|
| Sham Comparator: Control<br>Control Group: Subjects are treated with a Sham Sensory Stimulation System at home for 60 minutes daily for up to 12 months. | Device: Sensory Stimulation System (GS120) - Sham<br>* Sensory Stimulation System (GS120) - Sham settings<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) at 12-Months | Function as measured by the ADCS-ADL | Assessed for endpoint at Screening/Baseline and 12-Month clinic visits | 
| Change from Baseline in Combined Statistical Test (CST) for Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) and Mini-Mental State Exam (MMSE) at 12-Months | Function and Cognition as measured by CST for ADCS-ADL and MMSE | Assessed for endpoint at Screening/Baseline and 12-Month clinic visits | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Key Secondary: Change from Baseline in Mini-Mental State Exam (MMSE) at 12 Months | Cognition as measured by MMSE | Assessed for endpoint at Screening/Baseline and 12-Month clinic visits | 
| Change from Baseline in Whole brain volume at 12-Months | Whole brain volume as measured by 3 Tesla (3T) Magnetic Resonance Imaging (MRI) | Assessed for endpoint at Screening/Baseline and 12-Month clinic visits | 
| Change from Baseline in Hippocampal volume at 12-Months | Hippocampal volume as measured by 3 Tesla (3T) Magnetic Resonance Imaging (MRI) | Assessed for endpoint at Screening/Baseline and 12-Month clinic visits | 
| Change from Baseline in Clinical Dementia Rating- Sum of Boxes (CDR-SB) at 12-Months | Global change in symptoms as measured by CDR | Assessed for endpoint at Screening/Baseline and 12-Month clinic visits | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alzheimer's Disease, Mild Cognitive Impairment, Dementia