NCT00888056

Brief Summary

Alzheimer's Disease (AD) is the most common cause of dementia for which no treatment has shown consistent efficacy to stop or slow down the disease. Recent report of enhancement of memory abilities by bilateral chronic deep brain stimulation (DBS) of the fornix in the hypothalamus suggests that neuromodulation of circuits involved in memory processes may have therapeutic implications in AD patients with memory decline. The primary objectives of this prospective, non-controlled, pilot study are to evaluate the feasibility and safety of DBS in AD patients with mild cognitive and memory impairment, and to evaluate the efficacy of DBS to slow down or stabilize this decline. Five patients with AD (DSM IV) diagnosed less than two years, with mild cognitive decline (MMSE 20-24), and specific impairment of episodic memory will be included in a 2-year period. The evaluation criteria for feasibility will be the proportion of patients undergoing the procedure, chronic stimulation and evaluation process without adverse event (AE). Efficacy will be evaluated using numerous cognitive and memory testing. Changes in behavioral and mood scales, and changes in hypothalamic functions (clinical, biological and hormonal assessment) will evaluate safety and tolerance. Clinical, neuro-psychological, biological and imaging assessment will be performed 3 and one month before and 3, 6, 12 and 24 months after surgery. Bilateral electrodes (Medtronic 3389) will be implanted, by MR-guided frame-based stereotaxy, in the hypothalamic part of the fornix, and then connected to the generator (Kinetra, Medtronic). Chronic high-frequency stimulation will be delivered immediately after surgery. The investigators expect to slow down, or to stabilize the spontaneous decline of MMSE and ADAS scores after 6, 12 and 24 months of stimulation. In case of efficacy, DBS might offer to AD patient the possibility to slow down/stabilize their symptoms, which no other treatment can currently offer, and to increase their quality of life.

Trial Health

55
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Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
5

participants targeted

Target at below P25 for phase_1

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 23, 2009

Completed
1 day until next milestone

First Posted

Study publicly available on registry

April 24, 2009

Completed
1 month until next milestone

Study Start

First participant enrolled

June 1, 2009

Completed
Last Updated

June 27, 2012

Status Verified

April 1, 2009

First QC Date

April 23, 2009

Last Update Submit

June 26, 2012

Conditions

Outcome Measures

Primary Outcomes (1)

  • Evaluation criteria for feasibility will be the proportion of patients undergoing the procedure, chronic stimulation and evaluation process without adverse event.

    once time

Secondary Outcomes (1)

  • Efficacy will be evaluated using numerous cognitive and memory testing. Neuro-imaging changes after stimulation will be evaluate by morphological MRI and functional imaging (PET). Changes in behavioral and mood scales: evaluate safety

    M-3, D-7, D7, M3, M6, M12, M24

Study Arms (1)

ARM A

EXPERIMENTAL

Bilateral chronic electrical stimulation of the hypothalamus/fornix

Procedure: Bilateral chronic electrical stimulation of the hypothalamus/fornix

Interventions

Clinical, neuro-psychological, biological and imaging assessment will be performed 3 and one month before and 3, 6, 12 and 24 months after surgery. Bilateral electrodes (Medtronic 3389) will be implanted, under local anesthesia, by MR-guided frame-based stereotaxy, in the hypothalamic part of the fornix, before its entry in the mamillary body (well defined on T2 weighted sequences). Intra-operative stimulation will be used to search adverse effects or acute effects. Electrodes will be connected to the generator (Kinetra, Medtronic) under general anesthesia. Chronic high-frequency stimulation will be delivered immediately after surgery.

ARM A

Eligibility Criteria

Age50 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • patients with AD (DSM IV) diagnosed less than 2 years
  • age between 50 and 65
  • mild cognitive decline (MMSE between 20 and 24)
  • specific impairment of episodic memory (evaluated by Grober\&Buschke scale)
  • able to give and sign an informed consent
  • affiliated to the French national health and pensions organization

You may not qualify if:

  • associated DSM I axis pathology
  • contra-indication to surgery or MRI
  • preoperative MRI abnormalities
  • retraction of consent by the patient
  • decision of the promoter to stop the study

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

CHU de Nice - 4 avenue Reine Victoria - Hôpital de Cimiez

Nice, Alpes-Maritimes, 06001, France

RECRUITING

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

DementiaBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesTauopathiesNeurodegenerative DiseasesNeurocognitive DisordersMental Disorders

Study Officials

  • Fontaine Denys, PhD

    CHU de Nice - Service de Neurochirurgie - Hôpital Pasteur - 30 av de la voie Romaine - 06 100 Nice

    PRINCIPAL INVESTIGATOR
  • ROBERT Philippe, PhD

    CHU de Nice - CM2R - Hôpital de cimiez- 4 av reine Victoria 06001 Nice

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Robert Philippe, PhD

CONTACT

Fontaine Denys, PhD

CONTACT

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 23, 2009

First Posted

April 24, 2009

Study Start

June 1, 2009

Last Updated

June 27, 2012

Record last verified: 2009-04

Locations