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

NCT00947934 | Withdrawn DMC

• 2 other identifiers: 09 - APN - 04AFSSAPS2009-A00318-49
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

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.

Conditions

Memory Disorders

Keywords

Alzheimer disease,hypothalamus,Deep Brain Stimulation

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.

  2012

Secondary Outcomes (1)

• - 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

  2012

Study Arms (1)

Deep brain stimulation

EXPERIMENTAL

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.

Device: Deep brain stimulation

Interventions

Deep brain stimulation DEVICE

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

Also known as: Hypothalamus/fornix stimulation, Medtronic 3389

Deep brain stimulation

Eligibility Criteria

• Age: 50 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Nice: lead

Study Sites (2)

CMR2 Hôpital de Cimiez

Nice, 06001, France

Location

Service de Neurochirurgie Hôpital Universitaire de Pasteur

Nice, 06100, France

Location

MeSH Terms

Conditions

Memory Disorders; Alzheimer Disease

Interventions

Deep Brain Stimulation

Condition Hierarchy (Ancestors)

Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Dementia; Brain Diseases; Central Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics; Surgical Procedures, Operative

Study Officials

• Denys Fontaine, PH

  Service de Neurochirurgie

  PRINCIPAL INVESTIGATOR

• Philippe Robert, PH PU

  CMR2

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 27, 2009
• First Posted: July 28, 2009
• Study Start: August 1, 2009
• Primary Completion: August 1, 2010
• Study Completion: August 1, 2012
• Last Updated: April 12, 2024

Record last verified: 2009-07

Locations

FR (2)