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

June 26, 2012 updated by: Centre Hospitalier Universitaire de Nice

Effect of Deep Brain Stimulation of the Hypothalamus/ Fornix on Memory Impairment in Patients With Alzheimer's Disease

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

5

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • France
    • Alpes-Maritimes
      • Nice, Alpes-Maritimes, France, 06001
        • Recruiting
        • CHU de Nice - 4 avenue Reine Victoria - Hôpital de Cimiez
        • Contact:
        • Contact:
        • Principal Investigator:
          • Robert Philippe, PhD
        • Principal Investigator:
          • FONTAINE Denys, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

50 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
once time

Secondary Outcome Measures

Outcome Measure
Time Frame
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
M-3, D-7, D7, M3, M6, M12, M24

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

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

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2009

Study Registration Dates

First Submitted

April 23, 2009

First Submitted That Met QC Criteria

April 23, 2009

First Posted (Estimate)

April 24, 2009

Study Record Updates

Last Update Posted (Estimate)

June 27, 2012

Last Update Submitted That Met QC Criteria

June 26, 2012

Last Verified

April 1, 2009

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 09-PP-01

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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