Encapsulated Cell Biodelivery of Nerve Growth Factor to Alzheimer´s Disease Patients

Study Overview
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Brief Summary
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Cholinergic neurons in the basal forebrain project widely to the cerebral cortex and hippocampus. These neurons depend on nerve growth factor (NGF) from their target areas for survival. Impaired NGF supply is part of the Alzheimer's disease (AD) pathology, and the degeneration of these neurons correlates with the cognitive decline in these patients. The objective of encapsulated cell biodelivery (ECB) is to maintain normal levels of NGF to support cholinergic function. NsGene's NGF secreting ECB device (NsG0202) combines the potential benefits of targeted gene therapy with the safety of a retrievable implantable device. The study is an open label, single centre, 12-month, dose-escalation phase Ib study in patients with mild to moderate AD. The primary objective is safety and tolerability, while secondary outcomes measure include cognition, behaviour, neuropsychology, activities of daily living (ADL), positron emission tomography (PET) imaging and electroencephalography (EEG).

Official Title
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An Open Label, Dose-Escalation Study of Encapsulated Cell Biodelivery of Nerve Growth Factor to the Cholinergic Basal Forebrain of Alzheimer´s Disease Patients

Conditions
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Alzheimer's Disease

Intervention / Treatment
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* Drug: Nerve Growth Factor


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 50-80 years All patients must fulfil the NINDNDS-ARDRA criteria of Alzheimer's disease. The subject must have a score between 15-24 inclusive, on the mini-mental state examination (MMSE). The subject must have a caregiver who is able and committed to assist the subject to comply with the trial protocol, and who is willing to provide the information required at assessment interviews. Informed consent must be obtained from the subject together with a close caregiver, in accordance with the requirements of the ethical committee. Exclusion Criteria: A diagnosis of Schizophrenia, Schizo-affective disorder or paranoid disorder according to DSM IV without any suspicion cognitive decline. Patients with the following co-existing medical conditions: History of seizures. Brain tumor including meningeoma. Clinically significant hepatic, renal, pulmonary, metabolic or endocrine disturbances. Clinically significant back pain. Bleeding disorders. Patients who, in the opinion of the investigator, are otherwise unsuitable for a trial of this type.

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 80 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nerve Growth Factor<br>Dose 1 | Drug: Nerve Growth Factor<br>* Encapsulated cell biodelivery of Nerve Growth Factor (NGF) to the basal forebrain nuclei of the brain by multiple implantable devices housing NGF-secreting human cells<br>|
| Experimental: Nerve Growth Factor 2<br>Dose 2 | Drug: Nerve Growth Factor<br>* Encapsulated cell biodelivery of Nerve Growth Factor (NGF) to the basal forebrain nuclei of the brain by multiple implantable devices housing NGF-secreting human cells<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events |  | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog) | Cognition using ADAS-Cog, neuropsychologic test battery | 12 months |