Frontotemporal DementiaFRONSTIMNCT05699330
Subgenual Cingulate Deep Brain STIMulation for Apathetic Behavioral Variant FRONtotemporal Dementia
A study testing Bilateral subgenual cingulate deep brain stimulation (SGC DBS) in people with Frontotemporal Dementia and Deep Brain Stimulation, run by University Health Network, Toronto at 1 site in Canada.
Trial summary
Frontotemporal dementia (FTD), the most common dementia in individuals younger than 60 years of age, has no disease-modifying treatment. Neuroimaging studies have revealed salience and default mode network dysfunction, frontotemporal atrophy and hypometabolism as pathophysiological hallmarks of behavioral variant FTD… Read more about this study
- Who is it for?
- Ages 40 to 85 years
- Conditions the study is for
- Frontotemporal Dementia, Deep Brain Stimulation
- What is being tested?
- Bilateral subgenual cingulate deep brain stimulation (SGC DBS)
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteCanada
- Study dates
- 12 Jan 2023to 12 Jan 2026
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Men and women aged 40-85 years
- Diagnosis of image-supported behavioral variant frontotemporal dementia according to NIC-FTD and NACC FTLD guidelines
- Apathy as one of the symptoms
- Stable dose of baseline FTD medications for at least 3 months
- The patient has an available caregiver or other appropriate knowledgeable informant who can reliably report on 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.
Who cannot join
- Meets diagnostic criteria for other psychiatric diagnosis
- Has other major Central Nervous System (CNS) disease that impairs motor, sensory or cognitive
- Alcohol or illegal substance dependence within last 12 months
- Other medical conditions which render anesthesia and surgery as unsafe as determined by neurosurgeon
- Contraindications for MRI scanning, including implanted metallic devices (e.g., non-MRI-safe cardiac pacemaker or neurostimulator; some artificial joints metal pins; surgical clips; or other implanted metal parts), or claustrophobia or discomfort in confined spaces.
- Has a medical condition requiring a repetitive MRI body scan
Show all 10Show fewer
- Requires chemotherapy for the treatment of malignancy or requiring chronic oral or intravenous (immunosuppressive or) steroid therapy
- Is unable to comply with study visit schedule and timeline
- Past significant intracranial surgery
- A female lactating or of child-bearing potential, with a positive pregnancy test or not using adequate contraception.
Trial locations and contacts
1 site in 1 country.
Canada1 site, 1 recruiting
- Recruiting
Toronto Western Hospital
Toronto, Ontario, M5T 2S8
Cletus Cheyuo, 6478076845, cletus.cheyuo@uhn.ca
Tasnuva Hoque, 4166035800 ext. 2797, tasnuva.hoque@uhnresearch.ca
About this study
Official title: Subgenual Cingulate Deep Brain Stimulation for Apathetic Behavioral Variant Frontotemporal Dementia - A Pilot Trial
Frontotemporal dementia (FTD), the most common dementia in individuals younger than 60 years of age, has no disease-modifying treatment. Neuroimaging studies have revealed salience and default mode network dysfunction, frontotemporal atrophy and hypometabolism as pathophysiological hallmarks of behavioral variant FTD (bvFTD). A key brain structure affected by bvFTD is the subgenual cingulate (SGC), which serves as a hub for multi-axonal projections to and from the ventromedial prefrontal, dorsal anterior cingulate, orbitofrontal, and dorsolateral frontal cortices, and limbic structures.
The disruption of these SGC projections in bvFTD result in the core clinical features of apathy, disinhibition, loss of empathy, compulsivity, hyperorality and loss of executive function. The central goal of this proposal is to use deep brain stimulation (DBS) for modulation of the SGC downstream projections to treat bvFTD. Investigators hypothesize that SGC DBS will drive activity in the dysfunctional networks, reverse hypometabolism, and potentially improve symptoms. To determine the physiologic effects and mechanisms of SGC DBS, investigators will assess cerebral metabolism by FDG-PET, connectivity by rsfMRI and MEG, atrophy by volumetric MRI, and neurodegenerative and neuroinflammatory biomarkers. The safety and preliminary efficacy data obtained in these patients will inform the possible future role of DBS in apathetic bvFTD.
Read the detailed description
Study Design:
This is a single-center prospective, open-label, non-blinded, non-randomized, pilot study designed to evaluate the safety of deep brain stimulation (DBS) of the subgenual cingulate (SGC) in subjects diagnosed with apathetic behavioral variant frontotemporal dementia (abvFTD). In addition, the physiological and clinical effects of DBS will be assessed by neuroimaging and neuropsychological testing.
Investigators hypothesize that:
- Bilateral subgenual cingulate deep brain stimulator implantation will be well-tolerated in apathetic behavioral variant frontotemporal dementia patients. In AIM 1 investigators will assess the safety of SGC DBS, by monitoring intraoperative and postoperative adverse events related to surgery and stimulation in abvFTD patients.
- Bilateral subgenual cingulate deep brain stimulation will modulate brain circuits that are dysfunctional in patients with apathetic behavioral variant frontotemporal dementia. In AIM 2 investigators will determine the physiological impact and mechanisms of action of SGC DBS in abvFTD, by assessing cerebral metabolism with ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) PET scans, functional connectivity with magnetoencephalography and resting state functional magnetic resonance imaging, cerebral atrophy with volumetric MRI, and plasma and cerebrospinal fluid biomarkers of neurodegeneration (glial fibrillar acidic protein and neurofilament light chain) and neuroinflammation (Olink inflammation panels I and II) in abvFTD patients.
- Bilateral subgenual deep brain stimulation may improve some of the six core clinical features of behavioral variant frontotemporal dementia. In AIM 3 investigators will assess the clinical consequences of SGC DBS abvFTD, by performing the following neuropsychological tests: Neuropsychiatric index (NPI) and Apathy Evaluation Scale - Clinician version (AES-C) for apathy, NPI for disinhibition, compulsivity and hyperorality; Interpersonal reactivity index (IRI) for loss of empathy; National Institutes of Health - Executive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research (NIHEXAMINER) and Trail making test - A and B (TMT) for executive function; Social Cognition and Emotional Assessment (SEA)/Mini-SEA), and Frontotemporal lobar degeneration-modified Clinical Dementia Rating-I (FTLD CDR-I) for cognitive impairment.
Experimental Approach:
Investigators propose a 3-year open-label, single-arm, phase I study of subgenual cingulate deep brain stimulation for apathetic behavioral variant frontotemporal dementia. In years 1-2 investigators will screen frontotemporal dementia patients and enrol a total of 6 subjects who meet the study inclusion criteria. Prior to SGC DBS surgery, the subjects will undergo baseline neuroimaging (FDG PET, rsfMRI, MEG, vMRI and tractography), measurement of plasma and neuroinflammation (multiplex proximity extension assay (PEA) technology using Olink Explore Inflammation I and II panels), optional lumbar puncture (according to patient preference) for CSF biomarkers of neurodegeneration (GFAP) and NfL assays), and neuropsychological testing (NPI, AES-C, IRI, NIH-EXAMINER, TMT, SEA/mini-SEA and FTLD CDR-I). At 2 weeks after surgery, the DBS device will be turned on, with subsequent programming sessions at 4 weeks, 6 weeks, 8 weeks, 10 weeks, 3 months, 6 months, 9 months, 12 months and 24 months post-DBS surgery to optimize therapy. During programming, the DBS stimulation parameters will be titrated with the patient's apathy score, measured by AES-C, which is a validated 18-item apathy scale that can be easily administered in 10-20 minutes during the programming session. Full neuropsychological testing (NPI, AES-C, IRI, NIH-EXAMINER, TMT, SEA/mini-SEA and FTLD CDR-I ) will be performed at baseline before DBS surgery, and at 3-months, 6-months, 12-months and 24-months post-DBS surgery. Measurement of plasma neuroinflammatory biomarkers (Olink inflammation panels I and II) will be done at baseline before DBS surgery, and at 3-months, 6-months, 9-months, 12-months and 24-months post-DBS surgery. Lumbar puncture to obtain CSF for biomarkers of neurodegeneration (GFAP and NfL) will be optional and will be offered at baseline before DBS surgery and at 12-months and 24-months post-DBS surgery. Neuroimaging studies (FDG PET, rsfMRI, MEG, and vMRI) will be done at baseline before DBS surgery, and at 6-months, 12-months and 24-months post-DBS surgery. The baseline assessments and postoperative follow up will take place at Toronto Western Hospital. Investigators anticipate to complete patient follow-up by the end of year 3. However, it is possible that the 24-month follow up of a few patients may extend into year 4, depending on when their DBS surgery is performed.
- Conditions
- Frontotemporal Dementia, Deep Brain Stimulation
- Being tested
- Bilateral subgenual cingulate deep brain stimulation (SGC DBS)
- Keywords
- Subgenual cingulate, Deep brain stimulation, Apathy, Behavioral variant
- Medical subject headings
- Frontotemporal Dementia, Lethargy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bilateral subgenual cingulate deep brain stimulation (SGC DBS)Device
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.
| Study group | Role | What they receive |
|---|---|---|
| Bilateral subgenual cingulate deep brain stimulation (SGC DBS) | Experimental | 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. Receives: Device: Bilateral subgenual cingulate deep brain stimulation (SGC DBS) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Treatment-related Adverse Events
Patients will be closely monitored for adverse events following DBS surgery with regular check-ups at 3-months, 6-months, 12-months and 24-months post-DBS surgery
Measured: 24 months
Secondary outcomes (11)
Apathy Evaluation Scale - Clinician version (AES-C)
Patients will regularly complete the 18-item AES-C to assess apathy at baseline and at follow up. The scores range from 18-72, with a score greater than 34 indicating apathy
Measured: Baseline before DBS surgery, and at 3-months, 6-months, 12-months and 24-months post-DBS surgery
Neuropsychiatric index (NPI)
At follow up, patients will regularly complete the NPI questionnaire, which assesses 12 domains of behavioral disturbances in dementia. The severity scale has scores ranging from 1 to 3 points (1=mild; 2=moderate; and 3=severe) and the scale for assessing caregiver distress has scores ranging from 0 to 5 points (0=no distress; 1=minimal distress; 2=mild distress; 3=moderate distress; 4=severe distress; and 5=extreme distress).
Measured: Baseline before DBS surgery, and at 3-months, 6-months, 12-months and 24-months post-DBS surgery
Interpersonal reactivity index (IRI)
Patients will regularly complete the IRI questionnaire at follow up. The IRI consists of 28-items answered on a 5-point Likert scale ranging from "Does not describe me well" to "Describes me very well". The measure has 4 subscales, each made up of 7 different items.
Measured: Baseline before DBS surgery, and at 3-months, 6-months, 12-months and 24-months post-DBS surgery
National Institutes of Health - Executive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research (NIH-EXAMINER)
At follow up, patients will regularly complete the NIH-EXAMINER battery, which generates 4 composite scores to measure overall executive dysfunction, cognitive control, working memory, and fluency.
Measured: Baseline before DBS surgery, and at 3-months, 6-months, 12-months and 24-months post-DBS surgery
Trail making test - A and B (TMT)
At follow up, patients will regularly undergo the rail making tests, which measure the cognitive domains of processing speed, sequencing, mental flexibility and visual-motor skills and executive function. A cut-off time of 300 seconds is generally used to discontinue test administration and is therefore the typical maximum score.
Measured: Baseline before DBS surgery, and at 3-months, 6-months, 12-months and 24-months post-DBS surgery
Social Cognition and Emotional Assessment (SEA)/Mini-SEA)
At follow up, patients will regularly undergo the SEA/Mini-SEA battery. The Social Cognition and Emotional Assessment (SEA) is designed to provide an overview of social cognition and other processes mediated by the orbital and medial frontal regions in people with frontotemporal dementia. It comprises five subtests (Max total score = 55).
Measured: Baseline before DBS surgery, and at 3-months, 6-months, 12-months and 24-months post-DBS surgery
Frontotemporal lobar degeneration-modified Clinical Dementia Rating-I (FTLD CDR-I)
At follow up, patients will regularly complete the FTLD CDR-I questionnaire, which is the classic six-domain CDR plus two domains (behavior and language), specific for FTLD. A rating of "0" indicates normal behavioral or language status, while ratings of "1," "2," and "3" denote mild, modest, and severe deficits, respectively.
Measured: Baseline before DBS surgery, and at 3-months, 6-months, 12-months and 24-months post-DBS surgery
Plasma neuroinflammatory biomarkers (Olink inflammation panels I and II)
Plasma will be obtain at follow up and used to measure neuroinflammatory biomarkers using the Olink inflammation panels I and II.
Measured: Baseline before DBS surgery, and at 3-months, 6-months, 12-months and 24-months post-DBS surgery
Cerebrospinal fluid biomarkers of neurodegeneration (GFAP and NfL)
Collection of cerebrospinal fluid by lumbar puncture will be optional. If a patient consents to have a lumbar puncture, cerebrospinal fluid will be obtained to measure biomarkers of neurodegeneration (GFAP and NfL).
Measured: Baseline before DBS surgery and at 12-months and 24-months post-DBS surgery
Neuroimaging studies (FDG PET, rsfMRI, MEG, and vMRI)
Advanced neuroimaging (FDG PET, rsfMRI, MEG, and vMRI) will be done at baseline and follow up to check for cerebral glucose metabolism, connectivity and cerebral atrophy.
Measured: Baseline before DBS surgery, and at 6-months, 12-months and 24-months post-DBS surgery
Free and Cued Selective Reminding Test (FCSRT)
At follow up, patients will regularly complete the FCSRT, which is a multi-trial memory test that uses a "selective reminding" paradigm.
Measured: Baseline before DBS surgery, and at 3-months, 6-months, 12-months and 24-months post-DBS surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2023
- Study start12 Jan 2023
- Primary completion12 Jan 2026 (estimated)
- Study completion12 Jan 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Frontotemporal DementiaStudies of the same condition, open and under way.
- More trials run by University Health Network, TorontoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Collaborators
- Weston Brain Institute
- Responsible party
- Principal investigator, Andres M. Lozano, University Health Network, Toronto
- Investigators
- Andres M Lozano, MD, PhD, Principal investigator, University Health Network, TorontoCarmela Tartaglia, MD, Principal investigator, University Health Network, TorontoCletus Cheyuo, MD, PhD, Study director, University Health Network, Toronto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05699330
- Sponsor's protocol ID
- 21-6126
- Acronym
- FRONSTIM
- Status last verified
- May 2023
- First submitted
- 16 Jan 2023
- Last updated
- 10 May 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Subgenual Cingulate Deep Brain Stimulation for Apathetic Behavioral Variant Frontotemporal Dementia - A Pilot Trial
- ClinicalTrials.gov ID
- NCT05699330
- Acronym / sponsor ID
- FRONSTIM / 21-6126
- Conditions
- Frontotemporal Dementia, Deep Brain Stimulation
- Keywords
- Subgenual cingulate, Deep brain stimulation, Apathy, Behavioral variant
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 6 participants (estimated)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Collaborators
- Weston Brain Institute
- Study start
- 12 Jan 2023 (actual)
- Primary completion
- 12 Jan 2026 (estimated)
- Study completion
- 12 Jan 2026 (estimated)
- First posted
- 26 Jan 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Frontotemporal dementia (FTD), the most common dementia in individuals younger than 60 years of age, has no disease-modifying treatment. Neuroimaging studies have revealed salience and default mode network dysfunction, frontotemporal atrophy and hypometabolism as pathophysiological hallmarks of behavioral variant FTD (bvFTD). A key brain structure affected by bvFTD is the subgenual cingulate (SGC), which serves as a hub for multi-axonal projections to and from the ventromedial prefrontal, dorsal anterior cingulate, orbitofrontal, and dorsolateral frontal cortices, and limbic structures.
The disruption of these SGC projections in bvFTD result in the core clinical features of apathy, disinhibition, loss of empathy, compulsivity, hyperorality and loss of executive function. The central goal of this proposal is to use deep brain stimulation (DBS) for modulation of the SGC downstream projections to treat bvFTD. Investigators hypothesize that SGC DBS will drive activity in the dysfunctional networks, reverse hypometabolism, and potentially improve symptoms. To determine the physiologic effects and mechanisms of SGC DBS, investigators will assess cerebral metabolism by FDG-PET, connectivity by rsfMRI and MEG, atrophy by volumetric MRI, and neurodegenerative and neuroinflammatory biomarkers. The safety and preliminary efficacy data obtained in these patients will inform the possible future role of DBS in apathetic bvFTD.
Detailed description
Study Design:
This is a single-center prospective, open-label, non-blinded, non-randomized, pilot study designed to evaluate the safety of deep brain stimulation (DBS) of the subgenual cingulate (SGC) in subjects diagnosed with apathetic behavioral variant frontotemporal dementia (abvFTD). In addition, the physiological and clinical effects of DBS will be assessed by neuroimaging and neuropsychological testing.
Investigators hypothesize that:
- Bilateral subgenual cingulate deep brain stimulator implantation will be well-tolerated in apathetic behavioral variant frontotemporal dementia patients. In AIM 1 investigators will assess the safety of SGC DBS, by monitoring intraoperative and postoperative adverse events related to surgery and stimulation in abvFTD patients.
- Bilateral subgenual cingulate deep brain stimulation will modulate brain circuits that are dysfunctional in patients with apathetic behavioral variant frontotemporal dementia. In AIM 2 investigators will determine the physiological impact and mechanisms of action of SGC DBS in abvFTD, by assessing cerebral metabolism with ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) PET scans, functional connectivity with magnetoencephalography and resting state functional magnetic resonance imaging, cerebral atrophy with volumetric MRI, and plasma and cerebrospinal fluid biomarkers of neurodegeneration (glial fibrillar acidic protein and neurofilament light chain) and neuroinflammation (Olink inflammation panels I and II) in abvFTD patients.
- Bilateral subgenual deep brain stimulation may improve some of the six core clinical features of behavioral variant frontotemporal dementia. In AIM 3 investigators will assess the clinical consequences of SGC DBS abvFTD, by performing the following neuropsychological tests: Neuropsychiatric index (NPI) and Apathy Evaluation Scale - Clinician version (AES-C) for apathy, NPI for disinhibition, compulsivity and hyperorality; Interpersonal reactivity index (IRI) for loss of empathy; National Institutes of Health - Executive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research (NIHEXAMINER) and Trail making test - A and B (TMT) for executive function; Social Cognition and Emotional Assessment (SEA)/Mini-SEA), and Frontotemporal lobar degeneration-modified Clinical Dementia Rating-I (FTLD CDR-I) for cognitive impairment.
Experimental Approach:
Investigators propose a 3-year open-label, single-arm, phase I study of subgenual cingulate deep brain stimulation for apathetic behavioral variant frontotemporal dementia. In years 1-2 investigators will screen frontotemporal dementia patients and enrol a total of 6 subjects who meet the study inclusion criteria. Prior to SGC DBS surgery, the subjects will undergo baseline neuroimaging (FDG PET, rsfMRI, MEG, vMRI and tractography), measurement of plasma and neuroinflammation (multiplex proximity extension assay (PEA) technology using Olink Explore Inflammation I and II panels), optional lumbar puncture (according to patient preference) for CSF biomarkers of neurodegeneration (GFAP) and NfL assays), and neuropsychological testing (NPI, AES-C, IRI, NIH-EXAMINER, TMT, SEA/mini-SEA and FTLD CDR-I). At 2 weeks after surgery, the DBS device will be turned on, with subsequent programming sessions at 4 weeks, 6 weeks, 8 weeks, 10 weeks, 3 months, 6 months, 9 months, 12 months and 24 months post-DBS surgery to optimize therapy. During programming, the DBS stimulation parameters will be titrated with the patient's apathy score, measured by AES-C, which is a validated 18-item apathy scale that can be easily administered in 10-20 minutes during the programming session. Full neuropsychological testing (NPI, AES-C, IRI, NIH-EXAMINER, TMT, SEA/mini-SEA and FTLD CDR-I ) will be performed at baseline before DBS surgery, and at 3-months, 6-months, 12-months and 24-months post-DBS surgery. Measurement of plasma neuroinflammatory biomarkers (Olink inflammation panels I and II) will be done at baseline before DBS surgery, and at 3-months, 6-months, 9-months, 12-months and 24-months post-DBS surgery. Lumbar puncture to obtain CSF for biomarkers of neurodegeneration (GFAP and NfL) will be optional and will be offered at baseline before DBS surgery and at 12-months and 24-months post-DBS surgery. Neuroimaging studies (FDG PET, rsfMRI, MEG, and vMRI) will be done at baseline before DBS surgery, and at 6-months, 12-months and 24-months post-DBS surgery. The baseline assessments and postoperative follow up will take place at Toronto Western Hospital. Investigators anticipate to complete patient follow-up by the end of year 3. However, it is possible that the 24-month follow up of a few patients may extend into year 4, depending on when their DBS surgery is performed.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Bilateral subgenual cingulate deep brain stimulation (SGC DBS) | Experimental | Device: Bilateral subgenual cingulate deep brain stimulation (SGC DBS)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. |
Who may qualify
- Ages
- 40 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Men and women aged 40-85 years
- Diagnosis of image-supported behavioral variant frontotemporal dementia according to NIC-FTD and NACC FTLD guidelines
- Apathy as one of the symptoms
- Stable dose of baseline FTD medications for at least 3 months
- The patient has an available caregiver or other appropriate knowledgeable informant who can reliably report on 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.
Key exclusion criteria (10 listed)
- Meets diagnostic criteria for other psychiatric diagnosis
- Has other major Central Nervous System (CNS) disease that impairs motor, sensory or cognitive
- Alcohol or illegal substance dependence within last 12 months
- Other medical conditions which render anesthesia and surgery as unsafe as determined by neurosurgeon
- Contraindications for MRI scanning, including implanted metallic devices (e.g., non-MRI-safe cardiac pacemaker or neurostimulator; some artificial joints metal pins; surgical clips; or other implanted metal parts), or claustrophobia or discomfort in confined spaces.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Bilateral subgenual cingulate deep brain stimulation (SGC DBS)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. | Device | Bilateral subgenual cingulate deep brain stimulation (SGC DBS) |
Primary outcome
Incidence of Treatment-related Adverse Events
Time frame: 24 months
Patients will be closely monitored for adverse events following DBS surgery with regular check-ups at 3-months, 6-months, 12-months and 24-months post-DBS surgery
11 secondary outcomes
Apathy Evaluation Scale - Clinician version (AES-C)
Time frame: Baseline before DBS surgery, and at 3-months, 6-months, 12-months and 24-months post-DBS surgery
Neuropsychiatric index (NPI)
Time frame: Baseline before DBS surgery, and at 3-months, 6-months, 12-months and 24-months post-DBS surgery
Interpersonal reactivity index (IRI)
Time frame: Baseline before DBS surgery, and at 3-months, 6-months, 12-months and 24-months post-DBS surgery
National Institutes of Health - Executive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research (NIH-EXAMINER)
Time frame: Baseline before DBS surgery, and at 3-months, 6-months, 12-months and 24-months post-DBS surgery
Trail making test - A and B (TMT)
Time frame: Baseline before DBS surgery, and at 3-months, 6-months, 12-months and 24-months post-DBS surgery
Social Cognition and Emotional Assessment (SEA)/Mini-SEA)
Time frame: Baseline before DBS surgery, and at 3-months, 6-months, 12-months and 24-months post-DBS surgery
Frontotemporal lobar degeneration-modified Clinical Dementia Rating-I (FTLD CDR-I)
Time frame: Baseline before DBS surgery, and at 3-months, 6-months, 12-months and 24-months post-DBS surgery
Plasma neuroinflammatory biomarkers (Olink inflammation panels I and II)
Time frame: Baseline before DBS surgery, and at 3-months, 6-months, 12-months and 24-months post-DBS surgery
Cerebrospinal fluid biomarkers of neurodegeneration (GFAP and NfL)
Time frame: Baseline before DBS surgery and at 12-months and 24-months post-DBS surgery
Neuroimaging studies (FDG PET, rsfMRI, MEG, and vMRI)
Time frame: Baseline before DBS surgery, and at 6-months, 12-months and 24-months post-DBS surgery
Free and Cued Selective Reminding Test (FCSRT)
Time frame: Baseline before DBS surgery, and at 3-months, 6-months, 12-months and 24-months post-DBS surgery
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 May 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andres M Lozano, MD, PhD principal investigator
University Health Network, Toronto
Carmela Tartaglia, MD principal investigator
University Health Network, Toronto
Cletus Cheyuo, MD, PhD study director
University Health Network, Toronto
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Bilateral subgenual cingulate deep brain stimulation (SGC DBS) in people with Frontotemporal Dementia and Deep Brain Stimulation, run by University Health Network, Toronto at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 10 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Cletus Cheyuo, MD, PhD (6478076845, cletus.cheyuo@uhn.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Treatment-related Adverse Events (time frame: 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 May 2023.