Vortioxetine for the Treatment of Mood and Cognitive Symptoms in Frontotemporal Dementia

Functional Neuroimaging to Examine Affective Symptoms and Cognition in Frontotemporal Dementia

The goal of this clinical trial is to learn if vortioxetine improves mood symptoms and cognition in patients with early-stage behavioral variant Frontotemporal Dementia (bvFTD). The main questions this study aims to answer are:

1. Do individuals with mood symptoms and bvFTD have brain changes and cognitive profiles that differ compared to individuals without bvFTD?
2. Do mood symptoms and cognition improve following treatment with vortioxetine?

Researchers will also determine whether there are changes in the brain associated with vortioxetine treatment.

Participants will:

• Undergo a screening visit that involves clinical assessments and laboratory tests
• Undergo an initial brain magnetic resonance imaging (MRI) and fluorodeoxyglucose (18F) Positron Emission Tomography (FDG PET) scan before starting treatment with vortioxetine
• Undergo memory and problem-solving tests before starting treatment with vortioxetine
• Undergo approximately 12 weeks of treatment with vortioxetine, during which time there will be regular contact and assessments with the study psychiatrist
• Undergo a repeat PET scan and repeat memory and problem-solving tests after 12 weeks of treatment with vortioxetine

Study Overview

• Status: Recruiting
• Conditions: Frontotemporal Degeneration; Frontotemporal Dementia; Frontotemporal Dementia, Behavioral Variant; Frontotemporal Dementia (FTD); Fronto-temporal Lobar Dementia; Fronto-temporal Dementia
• Intervention / Treatment: Drug: Vortioxetine

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Christopher B Morrow, MD; Phone Number: 410-502-6509; Email: cmorrow3@jhmi.edu

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Recruiting
      • The Johns Hopkins Hospital
      • Contact: Christopher B Morrow, MD; Phone Number: 410-502-6509; Email: cmorrow3@jhmi.edu
      • Principal Investigator: Christopher B Morrow, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

FTD Patients

Inclusion Criteria:

1. Male or Female
2. Age 45 and above
3. Diagnosis of possible or probable bvFTD based on international consensus criteria for behavioral variant FTD (FTDC)
4. The presence of at least one of the following affective symptoms on the 12-item Neuropsychiatric Inventory: depression, anxiety, irritability, or agitation
5. A global Clinical Dementia Rating (CDR®) plus National Alzheimer's Coordinating Center (NACC) Frontotemporal lobar degeneration (FTLD) Behavior and Language Domains global score (CDR® plus NACC FTLD) less than or equal to one
6. Patients must be medically stable
7. Vortioxetine treatment is clinically indicated
8. Competent to provide informed consent

Exclusion Criteria:

1. No history of drug or alcohol dependence within six months prior to study entry
2. Negative toxicology screening for drugs of abuse
3. Subject must not be pregnant or nursing
4. No contraindications to Vortioxetine treatment
5. No contraindications for Magnetic Resonance (MR) scanning (e.g. metal implanted in the body)

Healthy Controls

Inclusion Criteria:

1. Male or Female
2. Age 45 and above
3. Subjects must be medically stable
4. Free of psychotropic medications
5. Competent to provide informed consent

Exclusion Criteria:

1. No current or past history of neurological or psychiatric illness or substance abuse
2. Subject must not be pregnant or nursing
3. Negative toxicology screening for drugs of abuse
4. No contraindications for MR scanning (e.g. metal implanted in the body)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patient Treatment Arm (Vortioxetine); Individuals with bvFTD and mood symptoms receiving the study drug, vortioxetine.	Drug: Vortioxetine; Individuals with bvFTD and mood symptoms will receive approximately 12 weeks of treatment with vortioxetine; Other Names: Trintellix

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in global cerebral glucose metabolism on [18F] fluorodeoxyglucose Positron Emission Tomography (FDG PET)	Cerebral glucose uptake measured through 18F FDG positron emission tomography	Baseline, 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in depressive symptoms as assessed by the Hamilton Depression Rating Scale (HDRS).	The HDRS is a widely used clinician-administered depression assessment tool designed to measure the severity of depression in individuals. It consists of 17 items rated on a 3 or 5 point scale with total scores ranging from 0 to 52. A higher score indicates more severe symptoms of depression.	Baseline, 12 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in performance on the Trail Making Test (TST).	The TMT is a widely used neuropsychological test that assesses an individuals cognitive abilities including executive function, attention, processing speed, and mental flexibility. It is divided into two parts: Trail Making Test A and Trail Making Test B. The Trail Making Test A primarily assesses visual attention and processing speed. Time taken to complete the task is recorded, with faster times indicating better cognitive performance. The Trail Making Test B primarily assesses cognitive flexibility, executive functioning, task switching and attention. Time taken to complete the task is recorded, with faster times indicating better cognitive performance.	Baseline, 12 weeks

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: National Institute on Aging (NIA); Lundbeck LLC
• Investigators: Principal Investigator: Christopher Morrow, MD, Johns Hopkins University

Study record dates

Study Major Dates

• Study Start (Actual): March 20, 2025
• Primary Completion (Estimated): May 31, 2029
• Study Completion (Estimated): September 1, 2029

Study Registration Dates

• First Submitted: September 17, 2024
• First Submitted That Met QC Criteria: September 17, 2024
• First Posted (Actual): September 19, 2024

Study Record Updates

• Last Update Posted (Actual): March 9, 2026
• Last Update Submitted That Met QC Criteria: March 5, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Antidepressant; Frontotemporal Dementia; FTD; Neuropsychiatric Symptoms
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Metabolic Diseases; Neurocognitive Disorders; Dementia; Neurodegenerative Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Frontotemporal Lobar Degeneration; Nutritional and Metabolic Diseases; Frontotemporal Dementia; Pick Disease of the Brain; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Piperazines; Vortioxetine
• Other Study ID Numbers: IRB00403796; 1K23AG088248 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All de-identified data will be preserved and shared in the National Archive of Computerized Data on Aging (NACDA).
• IPD Sharing Time Frame: Data will shared 12 months after study starts and every 6 months thereafter. All data will be shared upon publication or at the end of the award period, whichever is sooner. For published studies, data will be shared when the pre- print is available. NACDA studies have digital object identifiers (DOI) to aid in findability. The investigators will include that DOI in relevant publications. NACDA will make decisions about how long to preserve the data, but that data archive has not deleted any deposited data up to now.
• IPD Sharing Access Criteria: Given that all data will be de-identified, the investigators do not plan to control access to the data or require a Data Use Agreement. Data submitted to NACDA that are evaluated as constituting a low disclosure risk are publicly released and available to download directly from the NACDA website. The investigators plan to prepare and submit the data in a de-identified format in order to minimize any disclosure risk and allow for public release through NACDA. NACDA performs an evaluation of all submitted data prior to release to ensure disclosure risks are minimized, and the investigators anticipate approval for public release of data without restriction through the NACDA website.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes