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Study of the Brain Stimulation Effect on Memory Impairment in Alzheimer Disease

Primary Purpose

Memory Disorders

Status
Unknown status
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
Deep brain stimulation
Sponsored by
Centre Hospitalier Universitaire de Nice
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Memory Disorders focused on measuring Alzheimer disease,hypothalamus,Deep Brain Stimulation

Eligibility Criteria

50 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients between 50 and 65 years of age,
  • Patients with Alzheimer disease (according to DSM-IV criteria)
  • Recent diagnosis of Alzheimer disease (less than 2 years ago)
  • Patients with a total score in "Mini Mental Test" between 20 and 24.
  • Patient with impaired performance of their occasional memory, estimated by the test of Grober and Buschke (according to the standards, according to the age, the sex and the sociocultural level).
  • Patients covered by Social Security
  • Patients willing to sign the proper consent forms

Exclusion Criteria:

  • associated DSM I axis pathology,
  • contra-indication to surgery or MRI,
  • preoperative MRI abnormalities
  • Withdrawal of patient consent
  • Study sponsor or investigator decision to suspend the study.
  • Diagnosis of a metabolic or hormonal disorder on the biological assessment realized during the inclusion.

Sites / Locations

  • CMR2 Hôpital de CimiezRecruiting
  • Service de Neurochirurgie Hôpital Universitaire de PasteurRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Deep brain stimulation

Arm Description

Electrodes (Medtronic 3389) will be implanted in a bilateral way , under local anesthesia, at fornix level in its way through the hypothalamus, very visible on the MRI just before its entrance to mammilary bodies. Electrodes will be connected under general anesthesia to the pectoral sub-cutaneous pacemaker. The electric chronic stimulation (180 Hz, 2-3 V, 120 ms) will be begun the day after the operation.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

- Efficacy : evaluated using cognitive and memory testing. - Global improvement : CGI and IADL - Neuro-imaging : MRI and functional imaging - Safety/tolerance : Changes in behavioral,in hypothalamic functions and assessment of adverse events

Full Information

First Posted
July 27, 2009
Last Updated
December 7, 2011
Sponsor
Centre Hospitalier Universitaire de Nice
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1. Study Identification

Unique Protocol Identification Number
NCT00947934
Brief Title
Study of the Brain Stimulation Effect on Memory Impairment in Alzheimer Disease
Official Title
Study of the Effect of the Chronic Electric Stimulation of the Hypothalamus/Fornix on Memory Impairment in Alzheimer Disease.
Study Type
Interventional

2. Study Status

Record Verification Date
July 2009
Overall Recruitment Status
Unknown status
Study Start Date
August 2009 (undefined)
Primary Completion Date
August 2010 (Actual)
Study Completion Date
August 2012 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Centre Hospitalier Universitaire de Nice

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Alzheimer's Disease (AD) is the most common cause of dementia. Today no treatment had 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 assess 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 including classical instrument used in AD clinical trials. Changes in behavioral 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.
Detailed Description
Alzheimer's Disease (AD) is the most common cause of dementia whom estimated prevalence rise to more than 5 millions in the US. AD patients display progressive impairment of episodic memory and instrumental signs including aphasia, apraxia, and agnosia, together with general cognitive decline, death occurring 6-9 years after diagnosis. Up to now, no treatment had shown consistent efficacy to stop or slow down the disease. Recently, it has been shown that memory abilities have been enhanced by bilateral chronic deep brain stimulation (DBS) of the fornix in the hypothalamus, in a patient initially treated for malignant obesity (Hamani C, Ann Neurol, 2008). This report showed that neuro-anatomic circuits involved in memory processes are reachable and can be modulated. This modulation 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. The secondary objectives are to determine which cognitive and memory aspects are improved, and the duration of the efficacy of DBS on AD symptoms. The inclusion criteria are: patients with AD (DSM IV) diagnosed less than two years, age between 50 and 65, with mild cognitive decline (MMSE between 20 and 24), and specific impairment of episodic memory (using the free and cued selective reminding test: FCSRT ), able to give and sign an informed consent. Patients with associated DSM I axis pathology, contra-indication to surgery or MRI, or preoperative MRI abnormalities will not be included. Five patients 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 including WAIS, MMSE, ADAS scales, TMT-A and TMT-B testing, language evaluation, FCSRT and Rey figure. CGI and IADL will evaluate global improvement. Neuro-imaging changes after stimulation will be evaluate by morphological MRI (hippocampal volume) and functional imaging (PET). Changes in behavioral and mood scales, and changes in hypothalamic functions (clinical, biological and hormonal assessment) will evaluate safety and tolerance. Experimental paradigm: 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). Intraoperative 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. Expected results and perspectives: Spontaneously, neuropsychological scores progressively decline with time in AD patients (MMSE 3-4 points decrease and ADAS 6 points increase per year). We expect to slow down, or to stabilize these 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Memory Disorders
Keywords
Alzheimer disease,hypothalamus,Deep Brain Stimulation

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
5 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Deep brain stimulation
Arm Type
Experimental
Arm Description
Electrodes (Medtronic 3389) will be implanted in a bilateral way , under local anesthesia, at fornix level in its way through the hypothalamus, very visible on the MRI just before its entrance to mammilary bodies. Electrodes will be connected under general anesthesia to the pectoral sub-cutaneous pacemaker. The electric chronic stimulation (180 Hz, 2-3 V, 120 ms) will be begun the day after the operation.
Intervention Type
Device
Intervention Name(s)
Deep brain stimulation
Other Intervention Name(s)
Hypothalamus/fornix stimulation, Medtronic 3389
Intervention Description
Electrodes (Medtronic 3389) will be implanted in a bilateral way , under local anesthesia, at fornix level in its way through the hypothalamus, very visible on the MRI just before its entrance to mammilary bodies. Electrodes will be connected under general anesthesia to the pectoral sub-cutaneous pacemaker. The electric chronic stimulation (180 Hz, 2-3 V, 120 ms) will be begun the day after the operation
Primary Outcome Measure Information:
Title
Evaluation criteria for feasibility will be the proportion of patients undergoing the procedure, chronic stimulation and evaluation process without adverse event.
Time Frame
2012
Secondary Outcome Measure Information:
Title
- Efficacy : evaluated using cognitive and memory testing. - Global improvement : CGI and IADL - Neuro-imaging : MRI and functional imaging - Safety/tolerance : Changes in behavioral,in hypothalamic functions and assessment of adverse events
Time Frame
2012

10. Eligibility

Sex
All
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients between 50 and 65 years of age, Patients with Alzheimer disease (according to DSM-IV criteria) Recent diagnosis of Alzheimer disease (less than 2 years ago) Patients with a total score in "Mini Mental Test" between 20 and 24. Patient with impaired performance of their occasional memory, estimated by the test of Grober and Buschke (according to the standards, according to the age, the sex and the sociocultural level). Patients covered by Social Security Patients willing to sign the proper consent forms Exclusion Criteria: associated DSM I axis pathology, contra-indication to surgery or MRI, preoperative MRI abnormalities Withdrawal of patient consent Study sponsor or investigator decision to suspend the study. Diagnosis of a metabolic or hormonal disorder on the biological assessment realized during the inclusion.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Denys Fontaine, PH
Phone
+33 492 03 84 50
Email
fontaine.d@chu-nice.fr
First Name & Middle Initial & Last Name or Official Title & Degree
Philippe Robert, PH PU
Phone
+33 4 92 03 47 70
Email
robert.ph@chu-nice.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Denys Fontaine, PH
Organizational Affiliation
Service de Neurochirurgie
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Philippe Robert, PH PU
Organizational Affiliation
CMR2
Official's Role
Principal Investigator
Facility Information:
Facility Name
CMR2 Hôpital de Cimiez
City
Nice
ZIP/Postal Code
06001
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Philippe Robert, PU PH
Phone
+33 4 92 03 47 70
Email
Robert.ph@chu-nice.fr
First Name & Middle Initial & Last Name & Degree
Philippe Robert, PU PH
Facility Name
Service de Neurochirurgie Hôpital Universitaire de Pasteur
City
Nice
ZIP/Postal Code
06100
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Denys Fonatine, PH
Phone
04 92 03 84 50
Email
fontaine.d@chu-nice.fr
First Name & Middle Initial & Last Name & Degree
Denys Fontaine, PH

12. IPD Sharing Statement

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Study of the Brain Stimulation Effect on Memory Impairment in Alzheimer Disease

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