Pharmacologically Modulating the Noradrenergic Arousal System to Reduce Freezing of Gait in Parkinson's Disease: a Multi-centre and Multi-modal Approach (AnTi-FREEZE)

The goal of this clinical trial is to learn if the medication atomoxetine can reduce freezing of gait in people with Parkinson's disease. The main questions it aims to answer is:

Does atomoxetine reduce the frequency or severity of freezing of gait? What role does noradrenaline play in freezing of gait?

Researchers will compare atomoxetine to a placebo to see if atomoxetine can improve freezing of gait in people with Parkinson's disease.

Participants will:

Visit the study site for measurements Take atomoxetine or placebo Perform walking assessments and undergo MRI Complete questionnaires about anxiety, stress, and quality of life

Study Overview

• Status: Recruiting
• Conditions: Freezing of Gait; Parkinson's Disease (PD); Freezing of Gait Symptoms in Parkinson Disease
• Intervention / Treatment: Drug: Atomoxetine; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 3

Contacts and Locations

Study Locations

• Netherlands
  • Gelderland
    • Nijmegen, Gelderland, Netherlands, 6525 GA
      • Recruiting
      • Radboudumc
      • Contact: Franka Goossens; Phone Number: +31243668426; Email: franka.goossens@radboudumc.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Aged 18 years or older;
• Diagnosis of idiopathic PD according to MDS Diagnostic Criteria;
• Stabilised on optimal dopaminergic PD treatment for a minimum of four weeks prior to the baseline visit (Visit 1) and for the duration of the trial;
• Presence of FOG symptoms on a daily basis;
• Ability to walk for 10-meters unaided in the dopaminergic ON-state;
• Ability to provide written informed consent in accordance with ICH-GCP and local regulations;
• Willing and able to undergo all clinical trial assessments.

Exclusion Criteria:

• Current and/or previous (within 3 months) participation in a clinical trial;
• Any contra-indications for undergoing MRI-scanning (e.g. claustrophobia or metal parts within the body such as DBS, an infusion pump or a pacemaker);
• Co-morbidity that significantly impacts ambulation (e.g. orthopaedic or rheumatological ailments);
• Severe cognitive impairment hampering the ability to comply with the study protocol;
• Active psychosis that would impact the ability to comply with the study protocol;
• Severe cardiovascular disorders: severe hypertension (Sustained (Sitting) hypertension of ≥180 mmHg systolic or ≥110 mmHg diastolic, defined by the average of three observations, each at least 3 minutes apart, with the participant having assumed the required position for at least 3 minutes), heart failure, arterial occlusive disease, angina, haemodynamically significant congenital heart disease, cardiomyopathies, myocardial infarction, potentially life-threatening arrhythmias, long QT interval syndrome (QTc > 500ms Bazett-formula) and channelopathies that in the opinion of the study PI would significantly compromise participant safety;
• Severe cerebrovascular disorders: cerebral aneurysm or recent/significant stroke;
• Hepatic or renal insufficiency that in the opinion of the Principal Investigator would impact on the ability of the participant to safely participate;
• Narrow angle glaucoma;
• (History of) pheochromocytoma;
• Use of noradrenergic agents;
• Use of CYP2D6 inhibitors (SSRIs, quinidine, terbinafine);
• Use of high dose salbutamol (or other beta2 agonists) that in the opinion of the Principal Investigator would impact on the ability of the participant to safely participate;
• Pregnancy and/or breastfeeding;
• Known hypersensitivity to atomoxetine.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Atomoxetine in visit 2 and placebo in visit 3	Drug: Atomoxetine; Single dose, 40mg atomoxetine, capsule; Drug: Placebo; Single dose, placebo (microcrystalline cellulose), capsule
Experimental: Placebo in visit 2 and atomoxetine in visit 3	Drug: Atomoxetine; Single dose, 40mg atomoxetine, capsule; Drug: Placebo; Single dose, placebo (microcrystalline cellulose), capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The percentage of time frozen in the dopaminergic OFF-state	Baseline, visit 2 (one week after baseline) and visit 3 (one week after visit 2).

Secondary Outcome Measures

Outcome Measure	Time Frame
The percentage of time frozen in the dopaminergic ON-state	Baseline, visit 2 (one week after baseline) and visit 3 (one week after visit 2).
The brain network integration-segregation coefficient	Visit 2 (one week after baseline) and visit 3 (one week after visit 2).

Collaborators and Investigators

• Sponsor: Radboud University Medical Center
• Collaborators: University of Waterloo; Macquarie University, Australia

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2026
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: December 16, 2025
• First Submitted That Met QC Criteria: December 31, 2025
• First Posted (Actual): January 5, 2026

Study Record Updates

• Last Update Posted (Actual): February 27, 2026
• Last Update Submitted That Met QC Criteria: February 24, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Synucleinopathies; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurodegenerative Diseases; Movement Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Parkinson Disease; Organic Chemicals; Amines; Propylamines; Atomoxetine Hydrochloride
• Other Study ID Numbers: R0007688A

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