Deep Brain Stimulation for Frontotemporal Dementia
(FRONSTIM Trial)
Recruiting in Palo Alto (17 mi)
Overseen byAndres M Lozano, MD, PhD
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: University Health Network, Toronto
Must be taking: FTD medications
Must not be taking: Chemotherapy, Steroids
Disqualifiers: Other psychiatric, CNS disease, others
No Placebo Group
Approved in 2 Jurisdictions
Trial Summary
What is the purpose of this trial?This trial is testing a brain implant that sends electrical signals to help people with a specific type of dementia that causes severe symptoms like apathy. The goal is to see if this treatment can improve their brain function and reduce symptoms.
Will I have to stop taking my current medications?
The trial requires that participants have been on a stable dose of their current FTD medications for at least 3 months, so you won't need to stop taking them.
What data supports the effectiveness of the treatment Bilateral subgenual cingulate deep brain stimulation (SGC DBS) for Frontotemporal Dementia?
Deep brain stimulation (DBS) has shown potential in treating cognitive and memory issues in Alzheimer's disease, with some studies suggesting it may slow disease progression and improve brain activity. While specific data for Frontotemporal Dementia is limited, the safety and potential benefits observed in Alzheimer's and Parkinson's disease provide some hope for its effectiveness in other dementias.
12345Is deep brain stimulation generally safe for humans?
Deep brain stimulation (DBS) has been studied for various conditions, including Parkinson's disease and Alzheimer's disease. While some adverse events (side effects) have been reported, such as cognitive and psychiatric changes, infections, and the need for additional surgeries, these are generally not severe, and the procedure is considered to have an acceptable safety profile in humans.
16789How is Bilateral subgenual cingulate deep brain stimulation (SGC DBS) different from other treatments for frontotemporal dementia?
SGC DBS is unique because it involves implanting electrodes in the brain to deliver electrical impulses, which is different from traditional drug treatments. This approach is experimental and has been used in other conditions like severe depression, focusing on specific brain areas to potentially alter mood and behavior.
1011121314Eligibility Criteria
This trial is for adults aged 40-85 with behavioral variant frontotemporal dementia, showing symptoms like apathy. They must have stable medication use for the past 3 months and a caregiver or decision-maker to consent. Exclusions include pregnancy, substance dependence, other major CNS diseases, past significant brain surgery, MRI contraindications like metal implants, and conditions making anesthesia risky.Inclusion Criteria
I have been diagnosed with a specific type of dementia affecting behavior.
I have someone who can reliably report on my daily activities and function.
The patient must also have a substitute decision maker, if different from caregiver, to sign the informed consent for participation in the study
+3 more
Exclusion Criteria
Is unable to comply with study visit schedule and timeline
I am a woman who could become pregnant and am not using effective birth control.
I have had major brain surgery in the past.
+7 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Pre-Surgery Baseline Assessment
Baseline neuroimaging, neuropsychological testing, and biomarker assessments are conducted before DBS surgery
4 weeks
Multiple visits (in-person)
Surgery and Initial Recovery
Bilateral subgenual cingulate deep brain stimulator implantation and initial recovery
2 weeks
Inpatient stay for surgery and recovery
Post-Surgery Programming and Monitoring
DBS device activation and programming sessions to optimize therapy, along with regular neuropsychological and biomarker assessments
24 months
Regular visits at 2 weeks, 4 weeks, 6 weeks, 8 weeks, 10 weeks, 3 months, 6 months, 9 months, 12 months, and 24 months
Follow-up
Participants are monitored for safety and effectiveness after treatment
24 months
Regular follow-up visits
Participant Groups
The study tests deep brain stimulation of the subgenual cingulate to treat frontotemporal dementia symptoms by activating dysfunctional networks in the brain. It will monitor changes in cerebral metabolism, connectivity, atrophy and biomarkers to evaluate safety and preliminary effectiveness.
1Treatment groups
Experimental Treatment
Group I: Bilateral subgenual cingulate deep brain stimulation (SGC DBS)Experimental Treatment1 Intervention
Deep Brain Stimulation (DBS) is a neurosurgical procedure involving the implantation of deep brain electrodes, connected via a subcutaneous extension wire, to an implantable pulse generator (IPG, or 'battery') that is implanted below the collarbone. All patients will receive deep brain stimulation (DBS) targeting the subgenual cingulate (SGC) bilaterally. No other changes to pre-existing treatment will be made. This is the only arm in this experiment.
Bilateral subgenual cingulate deep brain stimulation (SGC DBS) is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Deep Brain Stimulation for:
- Parkinson's disease
- Essential tremor
- Dystonia
- Obsessive-compulsive disorder
- Medically refractory epilepsy
🇪🇺 Approved in European Union as Deep Brain Stimulation for:
- Parkinson's disease
- Essential tremor
- Dystonia
- Obsessive-compulsive disorder
- Medically refractory epilepsy
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Toronto Western HospitalToronto, Canada
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Who Is Running the Clinical Trial?
University Health Network, TorontoLead Sponsor
Weston Brain InstituteCollaborator
References
Deep brain stimulation for dementias. [2020]OBJECTIVE The aim of this article is to review the authors' and published experience with deep brain stimulation (DBS) therapy for the treatment of patients with Alzheimer's disease (AD) and Parkinson's disease dementia (PDD). METHODS Two targets are current topics of investigation in the treatment of AD and PDD, the fornix and the nucleus basalis of Meynert. The authors reviewed the current published clinical experience with attention to patient selection, biological rationale of therapy, anatomical targeting, and clinical results and adverse events. RESULTS A total of 7 clinical studies treating 57 AD patients and 7 PDD patients have been reported. Serious adverse events were reported in 6 (9%) patients; none resulted in death or disability. Most studies were case reports or Phase 1/2 investigations and were not designed to assess treatment efficacy. Isolated patient experiences demonstrating improved clinical response after DBS have been reported, but no significant or consistent cognitive benefits associated with DBS treatment could be identified across larger patient populations. CONCLUSIONS PDD and AD are complex clinical entities, with investigation of DBS intervention still in an early phase. Recently published studies demonstrate acceptable surgical safety. For future studies to have adequate power to detect meaningful clinical changes, further refinement is needed in patient selection, metrics of clinical response, and optimal stimulation parameters.
Deep brain stimulation for the treatment of Alzheimer disease and dementias. [2022]To review the use of deep brain stimulation (DBS) for treatment of dementia.
Modifying the progression of Alzheimer's and Parkinson's disease with deep brain stimulation. [2021]At times of an aging population and increasing prevalence of neurodegenerative disorders, effective medical treatments remain limited. Therefore, there is an urgent need for new therapies to treat Alzheimer's disease (AD). Deep brain stimulation (DBS) is thought to address the neuronal network dysfunction of this disorder and may offer new therapeutic options. Preliminary evidence suggests that DBS of the fornix may have effects on cognitive decline, brain glucose metabolism, hippocampal volume and cortical grey matter volume in certain patients with mild AD. Rodent studies have shown that increase of cholinergic neurotransmitters, hippocampal neurogenesis, synaptic plasticity and reduction of amyloid plaques are associated with DBS. Currently a large phase III study of fornix DBS is assessing efficacy in patients with mild AD aged 65 years and older. The Nucleus basalis of Meynert has also been explored in a phase I study in of mild to moderate AD and was tolerated well regardless of the lack of benefit. Being an established therapy for Parkinson's Disease (PD), DBS may exert some disease-modifying traits rather than being a purely symptomatic treatment. There is evidence of dopaminergic neuroprotection in animal models and some suggestion that DBS may influence the natural progression of the disorder. Neuromodulation may possibly have beneficial effects on course of different neurodegenerative disorders compared to medical therapy alone. For dementias, functional neurosurgery may provide an adjunctive option in patient care. This article is part of the special issue entitled 'The Quest for Disease-Modifying Therapies for Neurodegenerative Disorders'.
Cholinergic Deep Brain Stimulation for Memory and Cognitive Disorders. [2023]Memory and cognitive impairment as sequelae of neurodegeneration in Alzheimer's disease and age-related dementia are major health issues with increasing social and economic burden. Deep brain stimulation (DBS) has emerged as a potential treatment to slow or halt progression of the disease state. The selection of stimulation target is critical, and structures that have been targeted for memory and cognitive enhancement include the Papez circuit, structures projecting to the frontal lobe such as the ventral internal capsule, and the cholinergic forebrain. Recent human clinical and animal model results imply that DBS of the nucleus basalis of Meynert can induce a therapeutic modulation of neuronal activity. Benefits include enhanced activity across the cortical mantle, and potential for amelioration of neuropathological mechanisms associated with Alzheimer's disease. The choice of stimulation parameters is also critical. High-frequency, continuous stimulation is used for movement disorders as a way of inhibiting their output; however, no overexcitation has been hypothesized in Alzheimer's disease and lower stimulation frequency or intermittent patterns of stimulation (periods of stimulation interleaved with periods of no stimulation) are likely to be more effective for stimulation of the cholinergic forebrain. Efficacy and long-term tolerance in human patients remain open questions, though the cumulative experience gained by DBS for movement disorders provides assurance for the safety of the procedure.
Increased cerebral metabolism after 1 year of deep brain stimulation in Alzheimer disease. [2021]The importance of developing unique, neural circuitry-based treatments for the cognitive and neuropsychiatric symptoms of Alzheimer disease (AD) was the impetus for a phase I study of deep brain stimulation (DBS) in patients with AD that targeted the fornix.
Multicenter study on deep brain stimulation in Parkinson's disease: an independent assessment of reported adverse events at 4 years. [2008]Ongoing adverse events (AEs) at 4-years postsurgery in 69 patients with advanced Parkinson's disease (PD) who received deep brain stimulation (DBS) of the subthalamic nucleus (STN) (n = 49) or the internal globus pallidus (GPi) (n = 20), in the framework of a subset of eight centers of a multicenter study, were analyzed by an independent ad hoc committee. At baseline, the patients' age, sex, disease duration, and clinical condition were virtually identical, as was the duration of follow-up. There were 64 AEs reported in 53% of STN DBS patients and eight AEs reported in 35% of GPi DBS patients. Most of the AEs were not deemed severe and were reported to be present "both with and without stimulation." The majority of the AEs affected patients' cognitive, psychiatric and behavioral status, as well as speech, gait, and balance, and most of these AEs occurred in STN DBS patients. When comparing patients who exhibited AEs with those who did not, it was found that in the STN DBS group, the patients with AEs had a longer disease duration, as well as more gait disorders and psychiatric disturbances at baseline.
Surgical adverse events of deep brain stimulation in the subthalamic nucleus of patients with Parkinson's disease. The learning curve and the pitfalls. [2022]Several surgical adverse events (SAEs) have been associated with Deep Brain Stimulation (DBS) of the subthalamic nucleus (STN) in Parkinson's Disease (PD) patients, leading to certain confusion about the risk/benefit ratio of this technique, and giving rise to the need of more and more extensive control studies over longer periods. The aim of this article is to identify and quantify the factors associated with the most frequent AEs from STN DBS in PD-diagnosed patients.
Complications in subthalamic nucleus stimulation surgery for treatment of Parkinson's disease. Review of 272 procedures. [2019]Deep brain stimulation (DBS) is a surgical technique used to alleviate symptoms in patients with advanced Parkinson's disease (PD). It is a reversible procedure and its effect is based on electrical modulation of the nervous system and has considerable advantages in morbidity-mortality when compared to lesion techniques such as thalamotomy and/or pallidotomy. The objective was to evaluate the adverse events during the surgical placement of leads in the subthalamic nucleus for the treatment of Parkinson's disease.
Bilateral deep brain stimulation of the fornix for Alzheimer's disease: surgical safety in the ADvance trial. [2023]OBJECT This report describes the stereotactic technique, hospitalization, and 90-day perioperative safety of bilateral deep brain stimulation (DBS) of the fornix in patients who underwent DBS for the treatment of mild, probable Alzheimer's disease (AD). METHODS The ADvance Trial is a multicenter, 12-month, double-blind, randomized, controlled feasibility study being conducted to evaluate the safety, efficacy, and tolerability of DBS of the fornix in patients with mild, probable AD. Intraoperative and perioperative data were collected prospectively. All patients underwent postoperative MRI. Stereotactic analyses were performed in a blinded fashion by a single surgeon. Adverse events (AEs) were reported to an independent clinical events committee and adjudicated to determine the relationship between the AE and the study procedure. RESULTS Between June 6, 2012, and April 28, 2014, a total of 42 patients with mild, probable AD were treated with bilateral fornix DBS (mean age 68.2 ± 7.8 years; range 48.0-79.7 years; 23 men and 19 women). The mean planned target coordinates were x = 5.2 ± 1.0 mm (range 3.0-7.9 mm), y = 9.6 ± 0.9 mm (range 8.0-11.6 mm), z = -7.5 ± 1.2 mm (range -5.4 to -10.0 mm), and the mean postoperative stereotactic radial error on MRI was 1.5 ± 1.0 mm (range 0.2-4.0 mm). The mean length of hospitalization was 1.4 ± 0.8 days. Twenty-six (61.9%) patients experienced 64 AEs related to the study procedure, of which 7 were serious AEs experienced by 5 patients (11.9%). Four (9.5%) patients required return to surgery: 2 patients for explantation due to infection, 1 patient for lead repositioning, and 1 patient for chronic subdural hematoma. No patients experienced neurological deficits as a result of the study, and no deaths were reported. CONCLUSIONS Accurate targeting of DBS to the fornix without direct injury to it is feasible across surgeons and treatment centers. At 90 days after surgery, bilateral fornix DBS was well tolerated by patients with mild, probable AD. Clinical trial registration no.: NCT01608061 ( clinicaltrials.gov ).
Autonomic arousal elicited by subcallosal cingulate stimulation is explained by white matter connectivity. [2019]Subcallosal cingulate deep brain stimulation (SCC DBS) is an experimental treatment for severe depression. Surgery is performed with awake patients and intraoperative stimulation produces acute behavioral responses in select contacts. While there have been reports on the relationship between acute intraoperative behaviors and their relation to the location of the contacts, there are no descriptions of the physiological changes that accompany them.
Deep brain stimulation of the subthalamic nucleus in Parkinson's disease: evaluation of active electrode contacts. [2019]The subthalamic nucleus is the preferred target for deep brain stimulation in patients with advanced Parkinson's disease. The site of permanent stimulation is the subject of ongoing debate, as stimulation both within and adjacent to the subthalamic nucleus may be effective.
Impact of brain shift on subcallosal cingulate deep brain stimulation. [2021]Deep brain stimulation (DBS) of the subcallosal cingulate (SCC) is an emerging experimental therapy for treatment-resistant depression. New developments in SCC DBS surgical targeting are focused on identifying specific axonal pathways for stimulation that are estimated from preoperatively collected diffusion-weighted imaging (DWI) data. However, brain shift induced by opening burr holes in the skull may alter the position of the target pathways.
Multiple sequential image-fusion and direct MRI localisation of the subthalamic nucleus for deep brain stimulation. [2017]Deep brain stimulation (DBS) is the treatment of choice for advanced Parkinson's disease. The target co-ordinates are traditionally calculated in relation to the intercommissural distance. Anterior (AC) and posterior commissures (PC) may be visualised by the means of ventriculography, CT or MRI.
[Analysis of antiparkinsonian drug reduction after bilateral subthalamic deep brain stimulation]. [2010]Bilateral deep brain stimulation of the subthalamic nuclei (STN) is a well-established and cost-effective treatment in advanced PD.