Trial Outcomes & Findings for Low Frequency Electrical Stimulation of the Fornix in Intractable Mesial Temporal Lobe Epilepsy (MTLE) (NCT NCT02383407)

Results Overview

The primary outcome is safety and tolerability of LFSF in participants with intractable MTLE with regards to memory function. The number of participants listed are those who had a significant changes in RAVLT score.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

6 participants

Primary outcome timeframe

1 year

Results posted on

2023-06-26

Participant Flow

Once screened and enrolled, all subjects underwent implantation of SEEG electrodes in both hippocampi orthogonally through the lateral temporal neocortex. 2 patients were excluded as one opted for temporal lobectomy, and the other for multiple hippocampal transections. The implanted subjects did not receive stimulation for 1-month postoperatively then were randomized to either 2-Hz or 5-Hz.

Participant milestones

Participant milestones
Measure	Stimulation Group 2 Hz Patient will be randomized to a stimulation group of 2 Hz using Medtronic deep brain stimulation device Medtronic Deep Brain Stimulation	Stimulation Group 5 Hz Patient will be randomized to a stimulation group of 5 Hz using Medtronic deep brain stimulation device Medtronic Deep Brain Stimulation
Overall Study STARTED	1	2
Overall Study COMPLETED	1	2
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	2 Hz n=1 Participants Patient will be randomized to a stimulation group of 2 Hz using Medtronic deep brain stimulation device	5 Hz n=2 Participants Patient will be randomized to a stimulation group of 5 Hz using Medtronic deep brain stimulation device	Total n=3 Participants Total of all reporting groups
Age, Continuous	36 years n=1 Participants	46 years n=2 Participants	42.7 years n=3 Participants
Sex: Female, Male Female	0 Participants n=1 Participants	1 Participants n=2 Participants	1 Participants n=3 Participants
Sex: Female, Male Male	1 Participants n=1 Participants	1 Participants n=2 Participants	2 Participants n=3 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Bilateral temporal lobe epilepsy	1 Participants n=1 Participants	2 Participants n=2 Participants	3 Participants n=3 Participants

PRIMARY outcome

Timeframe: 1 year

The primary outcome is safety and tolerability of LFSF in participants with intractable MTLE with regards to memory function. The number of participants listed are those who had a significant changes in RAVLT score.

Outcome measures

Outcome measures
Measure	2 Hz n=1 Participants Patient will be randomized to a stimulation group of 2 Hz using Medtronic deep brain stimulation device	5 Hz n=2 Participants Patient will be randomized to a stimulation group of 5 Hz using Medtronic deep brain stimulation device
Safety and Tolerability of Low Frequency Stimulation of the Fornix With Regards to Memory Function	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 1 year

Since LFSF is expected to activate limbic structures, we will assess the effects of LFS on psychiatric symptoms using standardized measures that are known to be sensitive to changes to surgical treatment of TLE. The number of participation listed are those who had a significant change in anxiety, depression, or suicidality based on a qualitative overview of the psychiatric assessments performed preoperatively and postoperatively.

Outcome measures

Outcome measures
Measure	2 Hz n=1 Participants Patient will be randomized to a stimulation group of 2 Hz using Medtronic deep brain stimulation device	5 Hz n=2 Participants Patient will be randomized to a stimulation group of 5 Hz using Medtronic deep brain stimulation device
Psychiatric Health (Effects of LFS on Psychiatric Symptoms Using Standardized Measures That Are Known to be Sensitive to Changes to Surgical Treatment of TLE)	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 1 year

The DBS leads are routinely implanted for patients with Parkinson's disease. Thus, we planned to implant Model 3389 DBS leads using the same technique of stereotactic implantation. A secondary aim of this trial is to standardize the implantation, the evoked potential and electric current determination procedures in preparation for a large-scale phase III trial. The number of participants with the outcome measure are those in whom bilateral hippocampal CCEPs were consistently present.

Outcome measures

Outcome measures
Measure	2 Hz n=1 Participants Patient will be randomized to a stimulation group of 2 Hz using Medtronic deep brain stimulation device	5 Hz n=2 Participants Patient will be randomized to a stimulation group of 5 Hz using Medtronic deep brain stimulation device
To Assess if Electrode Implantation in the Fornix is Feasible as is Done in Patients With Parkinson's Disease.	1 Participants	2 Participants

SECONDARY outcome

Timeframe: 1 year

Population: arms were combined for safety reasons.

Seizure reduction: Subjects underwent implantation of pulse generators and long-term low-frequency stimulation with mean monthly seizures during blinded phase

Outcome measures

Outcome measures
Measure	2 Hz n=3 Participants Patient will be randomized to a stimulation group of 2 Hz using Medtronic deep brain stimulation device	5 Hz n=3 Participants Patient will be randomized to a stimulation group of 5 Hz using Medtronic deep brain stimulation device
Effect on Seizure Frequency	0.96 Seizure per week Standard Deviation 1.23	3.14 Seizure per week Standard Deviation 2.67

SECONDARY outcome

Timeframe: 1 year

Population: arms were combined for safety reasons.

Seizure reduction: Subjects underwent implantation of pulse generators and long-term low-frequency stimulation with mean monthly seizures during blinded phase

Outcome measures

Outcome measures
Measure	2 Hz n=3 Participants Patient will be randomized to a stimulation group of 2 Hz using Medtronic deep brain stimulation device	5 Hz n=3 Participants Patient will be randomized to a stimulation group of 5 Hz using Medtronic deep brain stimulation device
Effect on Seizure Frequency	0.96 Seizure per week Standard Deviation 1.23	3.14 Seizure per week Standard Deviation 2.67

Adverse Events

2 Hz

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

5 Hz

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	2 Hz n=1 participants at risk Patient will be randomized to a stimulation group of 2 Hz using Medtronic deep brain stimulation device	5 Hz n=2 participants at risk Patient will be randomized to a stimulation group of 5 Hz using Medtronic deep brain stimulation device
Nervous system disorders Intraparenchymal hemorrhage	0.00% 0/1 • Adverse events were recorded at each follow up visit, after implantation of the divide, follow-up was every 2 months for 12 months, then less regularly during the post blinding period for 12 months. Participants also reached out directly to the team between follow ups if they were to have any adverse events. Adverse events were recorded at each follow up visit as detailed above.	50.0% 1/2 • Number of events 1 • Adverse events were recorded at each follow up visit, after implantation of the divide, follow-up was every 2 months for 12 months, then less regularly during the post blinding period for 12 months. Participants also reached out directly to the team between follow ups if they were to have any adverse events. Adverse events were recorded at each follow up visit as detailed above.

Other adverse events

Adverse event data not reported

Additional Information

Dr. Mohamad Koubeissi

George Washington University

Phone: 202-741-2533

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place