Vortioxetine for Depressive Symptoms and Freezing of Gait in Parkinson Disease

February 3, 2025 updated by: Marianna Amboni

An Open Study to Evaluate the Efficacy of Vortioxetine on Freezing of Gait in Patients Affected by Parkinson Disease with Depressive Symptoms

The present study involves patients with Parkinson Disease (PD) suffering from freezing of gait (FOG) and depressive symptoms. The main aim of the study is evaluating the efficacy of vortioxetine in reducing moderate/severe FOG not responsive to dopaminergic treatment in patients with PD with depressive symptoms.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Depression and anxiety are common in patients with Parkinson's disease (PD). In PD, several drugs, such as dopamine-agonists, inhibitors of serotonin uptake (SSRI), tricyclic antidepressants (TCAs) and norepinephrine uptake inhibitors (SNRI) are effective in treating depressive symptoms. Recently, a Delphi consensus has concluded that multimodal drugs, like vortioxetine, are good treatment options for depression in PD and an open-label prospective study has shown that the vortioxetine may improve depressive symptoms and cognition in PD patients with major depression Vortioxetine has different mechanisms of action; it is a serotonin transporter (SERT) inhibitor, an antagonist of 5-HT3, 5-HT7, 5-HTID, a partial agonist of 5-HT1B and a full agonist of 5-HT1A. Moreover, despite vortioxetine does not interact significantly with the norepinephrine transporters or dopamine transporters, it has been shown to increase extracellular levels of norepinephrine, dopamine, and non-monoamine neurotransmitters including acetylcholine. These effects are likely related to the interaction between vortioxetine and various serotonin receptors.

Depression and anxiety or panic attacks are commonly associated to freezing of gait (FOG) in PD. FOG is a disabling symptom of parkinsonian syndromes, whose pathophysiology is heterogeneous and partly unclear. The relationship between FOG and dopaminergic treatment is rather complex. Based on response to dopaminergic treatment, FOG may be responsive, unresponsive (or partially responsive) or induced by dopaminergic drugs. FOG, especially unresponsive FOG, is commonly associated with cognitive dysfunction, namely attentional-executive and visuospatial alterations in PD patients. Since FOG episodes might be related to the Off state and/or to dopaminergic underdosing in PD, the first treatment option should be the increase of dopaminergic drugs dose, when possible. FOG episodes that are less responsive or nonresponsive to dopaminergic treatment represent the greatest therapeutic challenge. Beyond dopaminergic pathway, non-dopaminergic networks, i.e. noradrenergic and cholinergic transmission, may play a role in the pathogenesis of FOG. We hypothesize that vortioxetine might be effective in treating FOG by enhancing both monoamine and non-monoamine neurotransmitters.

STUDY DESIGN Clinical evaluation will be performed during optimal on state of patients

VISIT 1:

  1. Enrolment: Informed consent signature

  2. Standardized gait analysis with wearable sensors:

    Patients will be videotaped and assessed with wearable sensors (Opal) while:

    A) Performing the Rating Instrument to Assess Festination and Freezing Gait in Parkinsonian Patients (RIAFFGPP) . In RIAFFGPP patients have to:

    i. Sit down on a chair set up in front of a door. ii. After 30 s, stand up and walk to a floor mark (40 x 40 cm) iii. Perform within the mark two 360° turns, clockwise (cw) and counter-clockwise (ccw) iiii. Open and walk through the door, turn outside, and come back to the chair

    B) Walking forward along a 10 m path during three conditions:

    i. self paced velocity ii. fastest as possible without running pace iii. self paced velocity with mental task (seven serial subtraction from 100 - counting aloud)

  3. Clinical Global Impression scale (patient and clinician)
  4. FOG Questionnaire referred to the on state
  5. New freezing of gait questionnaire (NFOG-Q)
  6. Falls Efficacy Scale

  7. Cognitive function assessment:

    • MMSE
    • MoCA
    • FiPaT
    • Raven Progressive Matrices
    • The Benton Judgment of Line Orientation Test (JLOT)
    • Rey auditory 15-word learning test
    • Babcock story (episodic memory)
    • Rey Complex Figure (copy and recall)
    • Stroop test
    • Trial making test
    • Cancellation attentional matrices
    • Phonological verbal fluency
    • Semantic verbal fluency
    • Frontal Assessment Battery
    • Constructional Apraxia
    • SAND-Denomination
  8. MDS-UPDRS
  9. BDI-II
  10. NPI
  11. Apathy Scale
  12. PDQ-8
  13. Blood pressure, heart rate
  14. Instruction to fill in a falls diary for the next 2 weeks

VISIT 2 (Start of treatment, after 14 days ± 3 days from Visit 1)

  1. Enrolled patients will start vortioxetine:

    Vortioxetine Schedule:

    Vortioxetine 5 mg: once a day after lunch for one week, After one week, Vortioxetine 10 mg once a day

  2. Instruction on filling in again a falls diary:

Four weeks after starting medication patients will fill in again a falls diary for the next 2 consecutive weeks

VISIT 3 (after 12 weeks ± 7 days from ):

  1. Standardized gait analysis with wearable sensors (see visit 1)

    • RIAFFGPP
    • Walking forward along a 10 m path during three conditions
  2. Clinical Global Impression scale (patient and clinician)
  3. FOG Questionnaire
  4. New freezing of gait questionnaire (NFOG-Q)
  5. Falls Efficacy Scale
  6. Cognitive function assessment (see visit 1)
  7. MDS-UPDRS or
  8. BDI-II
  9. NPI
  10. Apathy Scale
  11. PDQ-8
  12. Blood pressure, heart rate
  13. Adverse events

Study Type

Interventional

Enrollment (Estimated)

40

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Marianna Amboni, Professor
  • Phone Number: +393358274695
  • Email: mamboni@unisa.it

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Diagnosis of PD according to published criteria
  2. Occurrence of depression according to Beck Depression Inventory II (score ≥ 15)
  3. A score ≥ 2 on the freezing question #2.13 of part 2 of the MDS-UPDRS (moderate-severe FOG).
  4. FOG not responsive to dopaminergic treatment.

Exclusion Criteria:

  1. Treatment with IMAO-B (rasagiline, selegiline, safinamide) (to be included, IMAO-B need to be withdrawn for at least 15 days)
  2. Concomitant treatment with other antidepressant drugs
  3. Hepatic and renal insufficiency
  4. Treatment with tramadol or triptans
  5. Psychotic disorder
  6. Dementia according to DSM-V

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: FOG-PD
FOG-PD will receive vortioxetine
Drug: Vortioxetine (tablet)
Vortioxetine will be used with the aim of treating freezing of gait in subjects with Parkinson Disease and depressive symptoms

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in the score of the Freezing Of Gait (FOG) Questionnaire referred to the "on state"
Time Frame: From enrollment to the end of treatment at 12 weeks
Total score of FOG Questionnaire ranges from 0 to 24 and higher scores correspond to more severe FOG
From enrollment to the end of treatment at 12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change on severity of FOG not responsive to dopaminergic treatment in patients with PD.
Time Frame: From enrollment to the end of treatment at 12 weeks
Change on duration (seconds) of FOG episodes on standardized gait analysis with wearable sensors
From enrollment to the end of treatment at 12 weeks
Chenage on frequency of FOG not responsive to dopaminergic treatment in patients with PD.
Time Frame: From enrollment to the end of treatment at 12 weeks
Change on number of FOG episodes on standardized gait analysis with wearable sensors
From enrollment to the end of treatment at 12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Marianna Amboni

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

February 1, 2025

Primary Completion (Estimated)

December 1, 2026

Study Completion (Estimated)

February 1, 2027

Study Registration Dates

First Submitted

January 16, 2025

First Submitted That Met QC Criteria

January 29, 2025

First Posted (Actual)

March 25, 2025

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

February 3, 2025

Last Verified

January 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ID:1279VTX - PD-20593T

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Clinical and outcome measures

IPD Sharing Time Frame

For 12 months after the completation of the study

IPD Sharing Access Criteria

contacting Central Contact Person by email on mamboni@unisa.it

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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