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

Centre Hospitalier Universitaire de Nice

Status and phase: Unknown; Phase 2; Phase 1

Conditions: Alzheimer's Disease

Treatments: Procedure: Bilateral chronic electrical stimulation of the hypothalamus/fornix

Study type: Interventional

Funder types: Other

Identifiers

NCT00888056

09-PP-01

Details and patient eligibility

About

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.

Enrollment: 5 estimated patients

Sex: All

Ages: 50 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

---

5 participants in 1 patient group

ARM A

Experimental group

Description:

Bilateral chronic electrical stimulation of the hypothalamus/fornix

Treatment:

Procedure: Bilateral chronic electrical stimulation of the hypothalamus/fornix