Subgenual Cingulate Deep Brain STIMulation for Apathetic Behavioral Variant FRONtotemporal Dementia

NCT05699330 | Unknown DMC

• 1 other identifier: 21-6126
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief 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 (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.

Conditions

Frontotemporal Dementia; Deep Brain Stimulation

Keywords

Subgenual cingulate; Deep brain stimulation; Apathy; Behavioral variant

Outcome Measures

Primary Outcomes (1)

• 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

  24 months

Secondary Outcomes (11)

• Apathy Evaluation Scale - Clinician version (AES-C)

  Baseline before DBS surgery, and at 3-months, 6-months, 12-months and 24-months post-DBS surgery

• Neuropsychiatric index (NPI)

  Baseline before DBS surgery, and at 3-months, 6-months, 12-months and 24-months post-DBS surgery

• Interpersonal reactivity index (IRI)

  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)

  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)

  Baseline before DBS surgery, and at 3-months, 6-months, 12-months and 24-months post-DBS surgery

Study Arms (1)

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.

Device: Bilateral subgenual cingulate deep brain stimulation (SGC DBS)

Interventions

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.

Bilateral subgenual cingulate deep brain stimulation (SGC DBS)

Eligibility Criteria

• Age: 40 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• University Health Network, Toronto: lead
• Weston Brain Institute: collaborator

Study Sites (1)

Toronto Western Hospital

Toronto, Ontario, M5T 2S8, Canada

RECRUITING

MeSH Terms

Conditions

Frontotemporal Dementia; Lethargy

Condition Hierarchy (Ancestors)

Frontotemporal Lobar Degeneration; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; TDP-43 Proteinopathies; Neurodegenerative Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Neurocognitive Disorders; Mental Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Andres M Lozano, MD, PhD

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

• Carmela Tartaglia, MD

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

• Cletus Cheyuo, MD, PhD

  University Health Network, Toronto

  STUDY DIRECTOR

Central Study Contacts

Cletus Cheyuo, MD, PhD

CONTACT

6478076845; cletus.cheyuo@uhn.ca

Tasnuva Hoque

CONTACT

416-603-5800; tasnuva.hoque@uhnresearch.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: University Professor

Study Record Dates

• First Submitted: January 16, 2023
• First Posted: January 26, 2023
• Study Start: January 12, 2023
• Primary Completion: January 12, 2026
• Study Completion: January 12, 2026
• Last Updated: May 10, 2023

Record last verified: 2023-05

Locations

CA (1)