| Registry | NCT07887737 |
|---|---|
| Status | Not yet recruiting |
| Phase | Not applicable |
| Study type | Interventional; randomized, sequential, masking: double, treatment |
| Enrollment | 6 (Estimated) |
| Sponsor | University of Texas Southwestern Medical Center (Other) |
| Conditions | Mild Cognitive Impairment (MCI), Mild Cognitive Impairment (MCI) Amnestic, Mild Cognitive Impairment (MCI) Due to Alzheimer's Disease, Memory Deficit, Memory Disorder |
| Interventions | Abbott St Jude Medical Infinity™ (Device) |
| Dates | start 2026-11-01 (estimated), primary completion 2027-10-01 (estimated), completion 2027-10-01 (estimated), first posted 2026-10-21, last updated 2026-10-21 |
Related Papers Related Patents Related Grants Related Experts
All trials for Mild Cognitive Impairment (MCI) All trials for Mild Cognitive Impairment (MCI) Amnestic All trials of Abbott St Jude Medical Infinity™
This trial is a 12-month safety and feasibility study, enrolling up to six participants. These participants will serve as their own controls, structured in multiple parts that follow an initial short-term stereo electroencephalography (SEEG) mapping period.
During this trial we aim to demonstrate the safety of acute and chronic network-guided stimulation in Mild Cognitive Impairment by evaluating adverse effects, tolerability, and feasibility during both the short- term SEEG mapping phase and subsequent permanent DBS therapy.
In addition to safety measures, therapeutic results as follows are to be tested for: (1) Develop patient-specific stimulation parameters for the treatment of MCI, as well as develop and test memory state classifiers by enrolling six individuals to undergo intracranial mapping (SEEG). We will use targeted memory tasks to generate neural data needed for state distinctions, and conduct a systematic parameter search to identify and develop optimal settings for each patient. (2) Assess efficacy of open loop stimulation by delivering a fixed open loop protocol based on the parameters discovered earlier, while SEEG electrodes remain in place, and testing the efficacy of the trained classifier to detect favorable brain states. (3) Evaluate chronic DBS therapy by implanting a permanent system in participants who show an acute beneficial response to assess long term outcomes. (4) Assess therapeutic outcomes and refine protocols by measuring reductions in memory-related impairment.
The above findings will guide further refinement of the device and protocol.
This is a 12-month, within-subject safety and feasibility study evaluating network-guided deep brain stimulation (DBS) for Mild Cognitive Impairment (MCI), enrolling up to six participants who serve as their own controls. The protocol proceeds through a screening phase, a short-term intracranial mapping period using stereo-electroencephalography (SEEG), permanent DBS implantation, an open-label programming phase, a double-blind discontinuation phase, and long-term follow-up.
Screening and Presurgical Baseline (up to 16 weeks before implantation). Eligible participants undergo a thorough standardized neuropsychological evaluation, including demographic and medical/psychiatric history, physical and mental status exams, vital signs, laboratory testing, and medication review (with specific attention to anti-amyloid monoclonal antibody therapy, which must be paused at least 12 weeks before surgery).
Participants undergo CT and 3T MRI imaging (structural, diffusion tractography, and resting-state functional sequences) for surgical planning. A presurgical baseline visit within 1-4 weeks of surgery repeats key labs, adds cardiac risk assessment (EKG, anesthesiology evaluation), confirms surgical clearance, and administers neuropsychological battery assessing processing speed, working memory, executive function, verbal and visual memory, and language.
SEEG Implantation and Inpatient Mapping (Day 0-7). Using standard stereotactic technique and ROSA planning software, 12 intracranial electrode trajectories (six per hemisphere) are placed targeting the anterior and posterior hippocampus, anterior and posterior cingulate cortex, anterior insula, and orbitofrontal cortex. Electrodes are measured using the NeuroPort recording system (Blackrock Microsystems, FDA-cleared under 510(k) K09095), sampling approximately 160 contacts at 2 kHz. All participants are monitored by the clinical staff, and maintained on antibiotics during admission.
Three experiments are conducted during the inpatient stay:
* Experiment 1 (Brain-state modeling): Participants perform memory tasks (CVLT-III, associative memory, serial recall, spatial navigation) to build patient-specific neural classifiers distinguishing favorable from unfavorable memory-related brain states.
* Experiment 2 (Parameter search): A grid-search paradigm delivers biphasic stimulation across target regions at varying amplitude (1-3 mA) and frequency, held within a fixed safety ceiling (200 µs pulse width, maximum charge density of 30 µC/cm²/phase, well under the Shannon safety criterion). Stimulation effects are evaluated against the classifier to identify parameters that shift brain activity toward a favorable memory state, with continuous epileptologist oversight for after-discharges and cardiopulmonary monitoring throughout.
* Experiment 3 (Open-loop stimulation): Using parameters identified in the search phase, two sessions combine a stimulation-free baseline with alternating active and sham stimulation blocks in a 2×2 design. Verbal memory (HVLT-R) and classifier-based neural biomarkers serve as outcome measures, reflecting the expectation that full therapeutic benefit may require weeks of chronic stimulation.
DBS Implantation (Day 7 ± 3 days). Participants meeting criteria proceed to explant of the SEEG electrodes and implantation of two permanent DBS leads (one per hemisphere, at sites selected from mapping data) along with a subcutaneous pulse generator, performed under general anesthesia with standard perioperative antibiotic prophylaxis. A post-procedure CT confirms absence of complications (e.g. hemorrhage) before discharge.
Postoperative Visits and Device Activation (Day 14 and Day 21). A one-week post-operative visit assesses wound healing and neurological status, with weekly follow-up thereafter for monitoring purposes. Approximately two weeks post-implant, device activation occurs using the rank-ordered parameter sets derived from inpatient testing. Predefined stopping/delay criteria apply (e.g., ≥4-point MoCA worsening confirmed at 48 hours, ≥10-point MADRS increase, or new suicidality), triggering deferral and biweekly reassessment until baseline status is re-established.
Open-Label Phase (Months 1-8). Programming is individualized based on inpatient-derived parameters, with amplitude titrated to balance benefit and side effects. Periodic visits track mood, cognition, and function (GAD-7, MADRS, C-SSRS, MoCA, ECog, CDR, CGI-S, HVLT-R), and the same stopping rules apply if worsening is observed on two consecutive visits, prompting stimulation cessation and supportive care.
Double-Blind Discontinuation (Weeks 33-45). All participants, regardless of open-label response, enter a blinded discontinuation period of up to 12 weeks to further characterize effects.
Long-Term Follow-Up. Participants are followed annually after completion of the blinded discontinuation phase to monitor device safety and intended clinical outcomes.
Across all phases, primary objectives are to characterize the safety, tolerability, and feasibility of acute (SEEG-based) and chronic (DBS) network-guided stimulation in MCI. Secondary objectives include developing patient-specific stimulation parameters and memory-state classifiers, testing open-loop stimulation efficacy, and evaluating longer-term cognitive and functional outcomes to inform refinement of the stimulation protocol and device.
| Arm | Type | Interventions | Description |
|---|---|---|---|
| Deactivation of Stimulation with the Abbott St Jude Medical Infinity™ | Placebo comparator | Device: Abbott St Jude Medical Infinity™ | Subjects will be deactivated (stimulation no longer occurs) from stimulation with the Abbott St Jude Medical Infinity™. Weekly assessments on primary memory measures will occur. |
| Stimulation Continuation with Abbott St Jude Medical Infinity™ | Experimental | Device: Abbott St Jude Medical Infinity™ | Subjects will continue stimulation (stimulation occurs) with the Abbott St Jude Medical Infinity™ based on parameters developed in the inpatient stay. Weekly assessments on primary memory measures will occur. |
Sex: All, ages: 60 Years to 85 Years
Inclusion Criteria:
1. Men and women (non-pregnant) between ages 60 and 85.
2. Meets NIA-AA core clinical criteria for MCI due to Alzheimer's Disease.
3. Determination by the investigator, based on clinical judgment and review of medical history, neurological examination, cognitive profile, and available clinical data, that Alzheimer's Disease is the primary suspected etiology.
4. Absence of other psychiatric or physical conditions that could interfere with the study.
5. Stable medication regimen for 4 weeks preceding surgery; participants currently receiving anti-amyloid therapies may enroll if they are able and willing to pause infusions for at least 12 weeks prior to study initiation and for the duration of the study.
6. Other medical conditions must be stable for at least 6 months prior to SEEG Implantation.
7. Able and willing to give informed consent or have a Legally Authorized Representative who is able to sign the informed consent form.
8. Able to have a study partner(s) or close relative(s) present for discussions about the study
Exclusion Criteria:
1. Active alcohol or substance use disorder within 6 months of entering the Screening Phase, excluding nicotine. Urine drug test positive for illicit drugs.
2. Neurological/Medical condition that makes the participant, in the opinion of the surgeon, a poor surgical candidate (e.g., progressive neurodegenerative disorder, significant cardiopulmonary disorder, need for chronic anticoagulation).
3. Any history of seizure disorder, hemorrhagic stroke, or has high risk of seizure (history of congenital brain malformation, neuro-developmental disorder , or other factors that predispose seizures such as an active eating disorder).
4. Cognitive symptoms that are not be better explained by delirium, unstable psychiatric illness, active substance use disorder, major untreated sleep disorder, acute neurologic illness, or other medical condition that, in the investigator's judgment, is the primary cause of the impairment.
5. Brain structural MRI abnormalities outside of expected pathology associated with Mild Cognitive Impairment.
6. Any medical contraindication to surgery such as infection.
7. Coagulopathy: Bleeding propensity and/or one of the following: INR > 1.5; prolonged activated partial thromboplastin time (aPTT) ≥ 45 sec; platelet count < 100×103 /uL
8. Uncontrolled hypertension (systolic > 145mmHg and/or diastolic > 90 mmHg), demonstrated on each of three repeated measurements taken within one hour regardless of whether or not the participant is taking antihypertensive medications.
9. Participation in another drug, device, or biological study within 90 days.
10. Current implanted neural stimulation devices including spinal cord stimulators and deep brain stimulators.
11. Need for Diathermy.
12. Chronic use of anticoagulant or anti-platelet agents that cannot be safely stopped for a sufficient duration (minimum 2.5 weeks) in the peri-operative period.
13. Any Psychiatric/Neurological/Medical condition that makes the participant, in the opinion of the Investigator, a poor candidate. These may be but are not limited to a DSM-5 diagnosis of schizophrenia, bipolar disorder, obsessive-compulsive disorder.
14. Moderate to severe depressive symptoms, defined as a GDS-15 score ≥11 at screening, or investigator judgment that depressive symptoms are unstable, severe, or likely to interfere with study participation or interpretation of cognitive outcomes.
15. High risk of suicide, defined as any of the following on the Columbia Suicide Severity Rating Scale (C-SSRS) short form at screening: active suicidal ideation with intent to act, active suicidal ideation with a specific plan and intent, suicidal behavior within the past 3 months or investigator judgment that the participant is at imminent or clinically significant risk for self-harm.
16. A separate cardiac condition that, in the opinion of a study physician, would present an unacceptable risk of undergoing general anesthesia.
17. Any clinical impression reflective of disease pathologies indicated by the list below is exclusionary
1. Frontotemporal degeneration spectrum disorders (e.g., behavioral-variant FTD, primary progressive aphasia)
2. Dementia with Lewy bodies / Parkinson disease dementia
3. Cerebral amyloid angiopathy (moderate to severe)
Eligibility Note:
Participants will be excluded if the investigator determines that cognitive impairment is primarily attributable to vascular cognitive impairment, Lewy body disease, frontotemporal degeneration, Parkinson's disease, traumatic brain injury, delirium, unstable psychiatric illness, medication effects, substance use, or another non-AD neurologic or systemic condition.
A prior or concurrent diagnosis of Alzheimer's disease is permitted only if the participant is clinically at the MCI / mild neurocognitive disorder stage, rather than dementia stage. In other words, participants with "MCI due to Alzheimer's disease," "prodromal Alzheimer's disease," or "early Alzheimer's disease" may be included if functional independence is preserved.