Ignite Creation Date:
2024-05-05 @ 9:43 PM
Last Modification Date:
2024-10-26 @ 10:08 AM
Study NCT ID:
NCT00947934
Status:
WITHDRAWN
Last Update Posted:
2024-04-12
First Post:
2009-07-27
Brief Title:
Study of the Brain Stimulation Effect on Memory Impairment in Alzheimer Disease
Sponsor:
Centre Hospitalier Universitaire de Nice
Organization:
Centre Hospitalier Universitaire de Nice
Study Overview
Official Title:
Study of the Effect of the Chronic Electric Stimulation of the HypothalamusFornix on Memory Impairment in Alzheimer Disease
Status:
WITHDRAWN
Status Verified Date:
2009-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
probleme of feasibility
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Alzheimers 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 downstabilize their symptoms which no other treatment can currently offer and to increase their quality of life
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 downstabilize their symptoms which no other treatment can currently offer and to increase their quality of life
Detailed Description:
Alzheimers 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 downstabilize their symptoms which no other treatment can currently offer and to increase their quality of life
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 downstabilize their symptoms which no other treatment can currently offer and to increase their quality of life
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| AFSSAPS2009-A00318-49 | None | None | None |