Chronic Electrical Stimulation of Hypothalamus/Fornix in Alzheimer's Disease

The recruitment status of this study is unknown because the information has not been verified recently.
Verified April 2009 by Centre Hospitalier Universitaire de Nice.
Recruitment status was  Recruiting
Sponsor:
Information provided by (Responsible Party):
Centre Hospitalier Universitaire de Nice
ClinicalTrials.gov Identifier:
NCT00888056
First received: April 23, 2009
Last updated: June 26, 2012
Last verified: April 2009
  Purpose

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.


Condition Intervention Phase
Alzheimer's Disease
Procedure: Bilateral chronic electrical stimulation of the hypothalamus/fornix
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Effect of Deep Brain Stimulation of the Hypothalamus/ Fornix on Memory Impairment in Patients With Alzheimer's Disease

Resource links provided by NLM:


Further study details as provided by Centre Hospitalier Universitaire de Nice:

Primary Outcome Measures:
  • Evaluation criteria for feasibility will be the proportion of patients undergoing the procedure, chronic stimulation and evaluation process without adverse event. [ Time Frame: once time ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 [ Time Frame: M-3, D-7, D7, M3, M6, M12, M24 ] [ Designated as safety issue: No ]

Estimated Enrollment: 5
Study Start Date: June 2009
Arms Assigned Interventions
Experimental: ARM A
Bilateral chronic electrical stimulation of the hypothalamus/fornix
Procedure: Bilateral chronic electrical stimulation of the hypothalamus/fornix
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.

  Eligibility

Ages Eligible for Study:   50 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00888056

Contacts
Contact: Robert Philippe, PhD +33492037993 robert.p@chu-nice.fr
Contact: Fontaine Denys, PhD +33492038450 fontaine.d@chu-nice.fr

Locations
France
CHU de Nice - 4 avenue Reine Victoria - Hôpital de Cimiez Recruiting
Nice, Alpes-Maritimes, France, 06001
Contact: ROBERT Philippe, PhD    +33492037993    robert.p@chu-nice.fr   
Contact: Fontaine Denys, PhD    +33492038450    fontaine.d@chu-nice.fr   
Principal Investigator: Robert Philippe, PhD         
Principal Investigator: Fontaine Denys, PhD         
Sponsors and Collaborators
Centre Hospitalier Universitaire de Nice
Investigators
Principal Investigator: 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
  More Information

No publications provided

Responsible Party: Centre Hospitalier Universitaire de Nice
ClinicalTrials.gov Identifier: NCT00888056     History of Changes
Other Study ID Numbers: 09-PP-01
Study First Received: April 23, 2009
Last Updated: June 26, 2012
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Additional relevant MeSH terms:
Alzheimer Disease
Brain Diseases
Central Nervous System Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Dementia
Mental Disorders
Nervous System Diseases
Neurodegenerative Diseases
Tauopathies

ClinicalTrials.gov processed this record on October 23, 2014