Dopaminergic Therapy for Frontotemporal Dementia Patients

NCT04937452 | Completed Phase 2

• 1 other identifier: EudraCT 2019-002997-30
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 3

Brief Summary

This is a phase IIa 24-week randomized, double-blind, placebo-controlled study. The study is designed to evaluate the efficacy and safety of Rotigotine (RTG) transdermal administration at the dosage of 4 mg or 6 mg per day versus Placebo (PLC) in newly diagnosed behavioural Frontotemporal Dementia (bvFTD) patients. 75 patients with a diagnosis of probable bvFTD will be randomly allocated to the 3 treatment arms (RTG 4mg/day, RTG 6mg/day or PLC), with 25 patients per group. Clinical and neurophysiological measurements and brain metabolism via FDG-PET will be collected before and after drug administration.

Conditions

Frontotemporal Dementia; Dementia; Aphasia, Primary Progressive; Pick Disease of the Brain; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Mental Disorders; Neurodegenerative Diseases; Frontotemporal Lobar Degeneration; TDP-43 Proteinopathies; Proteostasis Deficiencies; Metabolic Disease; Aphasia; Speech Disorders; Language Disorders; Communication Disorders; Neurobehavioral Manifestations; Neurologic Manifestations

Keywords

dopamine; frontal cortex; FTD; Rotigotine

Outcome Measures

Primary Outcomes (1)

• Frontal Assessment Battery (FAB)

  Battery to evaluate executive functions. The scores range from 0-18 with a higher score meaning less cognitive impairment.

  24 weeks

Secondary Outcomes (15)

• Neuropsychiatric Inventory (NPI) scale

  24 weeks

• Frontal Behavioural Inventory (FBI)

  24 weeks

• Clinical Dementia Rating scale-Frontotemporal dementia Sum Of Boxes (CDR-FTDSOB)

  24 weeks

• Screening for aphasia in Neurodegeneration (SAND) scale

  24 weeks

• Mini Mental State Examination (MMSE)

  24 weeks

Study Arms (3)

Rotigotine 4 mg

EXPERIMENTAL

Rotigotine 4 mg/24 hours transdermal patch administration

Drug: Rotigotine 4Mg/24Hrs Patch

Rotigotine 6 mg

EXPERIMENTAL

Rotigotine 6 mg/24 hours transdermal patch administration

Drug: Rotigotine 6Mg/24Hrs Patch

Placebo

PLACEBO COMPARATOR

Placebo transdermal patch administration

Drug: Placebo

Interventions

Rotigotine 4Mg/24Hrs Patch DRUG

Rotigotine 4 mg/24Hrs administration for 24 weeks

Also known as: Neupro

Rotigotine 4 mg

Rotigotine 6Mg/24Hrs Patch DRUG

Rotigotine 6 mg/24Hrs administration for 24 weeks

Also known as: Neupro

Rotigotine 6 mg

Placebo DRUG

Placebo administration for 24 weeks

Placebo

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The patient has a diagnosis of probable Frontotemporal dementia behavioural variant (bv-FTD) based on the International consensus clinical diagnostic criteria described by Rascovsky et al., 2011.
• The patient is a man or a woman, aged from 40 to 80 years.
• The patient has a Clinical Dementia Rating-FTD (CDR-FTD) total score of ≤2 at Screening.
• The patient has not been treated with acetylcholinesterase inhibitor (AChEI), i.e., donepezil, galantamine, or rivastigmine, at the time of screening.
• The patient is able to comply with the study procedures in the view of the investigator.
• Evidence of frontotemporal hypometabolism at PET imaging.
• Evidence of amyloid markers excluding Alzheimer's disease (cerebrospinal fluid Abeta/Tau dosages or amyloid PET imaging).
• Signature and date of written ICF prior to entering in the study
• Female patient must be neither pregnant nor breastfeeding. Women of childbearing potential should be willing to use contraception while receiving Rotigotine and for six months after its last assumption

You may not qualify if:

• Significant neurodegenerative disorder of the central nervous system other than FTD e.g., Alzheimer's disease, Lewy body dementia, Parkinson's disease, multiple sclerosis, progressive supranuclear palsy, normal pressure hydrocephalus, Huntington's disease, any condition directly or indirectly caused by Transmissible Spongiform Encephalopathy (TSE), Creutzfeldt-Jakob Disease (CJD), variant Creutzfeldt-Jakob Disease (vCJD), or new variant Creutzfeldt-Jakob Disease (nvCJD)
• Significant intracranial focal or vascular pathology seen on brain MRI scan within a maximum of 6 months before Baseline leading to a diagnosis other than probable FTD.
• The patients has history of seizure (with the exception of febrile seizures in childhood).
• Metal implants in the head (except dental), pacemaker, cochlear implants, or any other non-removable items that are contraindications to MR imaging.
• Treatment currently or within 3 months before Baseline with any of the following medications: Typical and Atypical antipsychotics (i.e., Clozapine, Olanzapine); Antiepileptics drugs (i.e., Carbamazepine, Primidone, Pregabalin, Gabapentin); Antidepressants (i.e., Citalopram, Duolxetine, Paroxetine).

Sponsors & Collaborators

• I.R.C.C.S. Fondazione Santa Lucia: lead
• Alzheimer's Drug Discovery Foundation: collaborator

Study Sites (3)

Giacomo Koch

Rome, <None>, 00179, Italy

Location

Department of Neurology, University of Brescia

Brescia, Italy

Location

Santa Lucia Foundation

Rome, 00179, Italy

Location

Related Publications (1)

• Koch G, Assogna M, Gadola Y, Alberici A, Di Lorenzo F, Bonni S, Borghi I, Cerulli Irelli E, Mencarelli L, Maiella M, Esposito R, Casula EP, Pezzopane V, D'Acunto A, Candeo F, Ferraresi M, Guerrera G, Battistini L, Premi E, Bracca V, Lucchini S, Bertagna F, Romano P, Ludovici A, Daniele A, Motta C, Ferrari C, Martorana A, Borroni B. Safety and efficacy of rotigotine in patients with frontotemporal dementia: a phase 2, double-blind, randomized, placebo-controlled, multicenter trial. Lancet Reg Health Eur. 2025 Aug 5;57:101409. doi: 10.1016/j.lanepe.2025.101409. eCollection 2025 Oct.

  PMID: 40809903 DERIVED

MeSH Terms

Conditions

Frontotemporal Dementia; Dementia; Aphasia, Primary Progressive; Pick Disease of the Brain; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Mental Disorders; Neurodegenerative Diseases; Frontotemporal Lobar Degeneration; TDP-43 Proteinopathies; Proteostasis Deficiencies; Metabolic Diseases; Aphasia; Speech Disorders; Language Disorders; Communication Disorders; Neurobehavioral Manifestations; Neurologic Manifestations

Interventions

rotigotine

Condition Hierarchy (Ancestors)

Nutritional and Metabolic Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurodevelopmental Disorders

Study Officials

• Giacomo Koch, MD

  Santa Lucia Foundation IRCCS

  PRINCIPAL INVESTIGATOR

• Martina Assogna, MD

  Santa Lucia Foundation IRCCS

  STUDY DIRECTOR

• Alessandro Martorana, MD, PhD

  University of Tor Vergata

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof

Study Record Dates

• First Submitted: June 16, 2021
• First Posted: June 24, 2021
• Study Start: June 3, 2021
• Primary Completion: December 30, 2023
• Study Completion: April 1, 2024
• Last Updated: October 22, 2024

Record last verified: 2022-07

Locations

IT (3)