Clinical trial NCT01163825: Encapsulated Cell Biodelivery of Nerve Growth Factor to Alzheimer´s Disease Patients
Official title: An Open Label, Dose-Escalation Study of Encapsulated Cell Biodelivery of Nerve Growth Factor to the Cholinergic Basal Forebrain of Alzheimer´s Disease Patients
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Alzheimer's Disease
Lead sponsor: NsGene A/S
Sponsor class: INDUSTRY
Collaborators: name: Karolinska Institutet
name: Region Stockholm
First posted: 2010-07-16
Enrollment: 6
Sex: ALL
Minimum age (years): 50
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: Inclusion Criteria:

1. Age 50-80 years
2. All patients must fulfil the NINDNDS-ARDRA criteria of Alzheimer's disease.
3. The subject must have a score between 15-24 inclusive, on the mini-mental state examination (MMSE).
4. 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.
5. Informed consent must be obtained from the subject together with a close caregiver, in accordance with the requirements of the ethical committee.

Exclusion Criteria:

1. A diagnosis of Schizophrenia, Schizo-affective disorder or paranoid disorder according to DSM IV without any suspicion cognitive decline.
2. Patients with the following co-existing medical conditions:
3. History of seizures.
4. Brain tumor including meningeoma.
5. Clinically significant hepatic, renal, pulmonary, metabolic or endocrine disturbances.
6. Clinically significant back pain.
7. Bleeding disorders.
8. Patients who, in the opinion of the investigator, are otherwise unsuitable for a trial of this type.

Primary outcomes:
measure: Adverse events
timeFrame: 12 months
Secondary outcomes:
measure: Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog)
timeFrame: 12 months
Other outcomes:
Locations:
city: Stockholm
country: Sweden
facility: Karolinska University Hospital
Study officials:
affiliation: Karolinska University Hospital
name: Maria E Jönhagen, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Machado A, Ferreira D, Grothe MJ, Eyjolfsdottir H, Almqvist PM, Cavallin L, Lind G, Linderoth B, Seiger A, Teipel S, Wahlberg LU, Wahlund LO, Westman E, Eriksdotter M; Alzheimer's Disease Neuroimaging Initiative. The cholinergic system in subtypes of Alzheimer's disease: an in vivo longitudinal MRI study. Alzheimers Res Ther. 2020 May 6;12(1):51. doi: 10.1186/s13195-020-00620-7.
citation: Eyjolfsdottir H, Eriksdotter M, Linderoth B, Lind G, Juliusson B, Kusk P, Almkvist O, Andreasen N, Blennow K, Ferreira D, Westman E, Nennesmo I, Karami A, Darreh-Shori T, Kadir A, Nordberg A, Sundstrom E, Wahlund LO, Wall A, Wiberg M, Winblad B, Seiger A, Wahlberg L, Almqvist P. Targeted delivery of nerve growth factor to the cholinergic basal forebrain of Alzheimer's disease patients: application of a second-generation encapsulated cell biodelivery device. Alzheimers Res Ther. 2016 Jul 7;8(1):30. doi: 10.1186/s13195-016-0195-9.
citation: Wahlberg LU, Lind G, Almqvist PM, Kusk P, Tornoe J, Juliusson B, Soderman M, Sellden E, Seiger A, Eriksdotter-Jonhagen M, Linderoth B. Targeted delivery of nerve growth factor via encapsulated cell biodelivery in Alzheimer disease: a technology platform for restorative neurosurgery. J Neurosurg. 2012 Aug;117(2):340-7. doi: 10.3171/2012.2.JNS11714. Epub 2012 Jun 1.