Dopaminergic Therapy for Frontotemporal Dementia Patients

Last updated: October 18, 2024
Sponsor: I.R.C.C.S. Fondazione Santa Lucia
Overall Status: Completed

Phase

2

Condition

Communication Disorders

Memory Loss

Multiple Sclerosis

Treatment

Placebo

Rotigotine 6Mg/24Hrs Patch

Rotigotine 4Mg/24Hrs Patch

Clinical Study ID

NCT04937452
EudraCT 2019-002997-30
  • Ages 40-80
  • All Genders

Study 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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  1. The patient has a diagnosis of probable Frontotemporal dementia behavioural variant (bv-FTD) based on the International consensus clinical diagnostic criteria describedby Rascovsky et al., 2011.

  2. The patient is a man or a woman, aged from 40 to 80 years.

  3. The patient has a Clinical Dementia Rating-FTD (CDR-FTD) total score of ≤2 atScreening.

  4. The patient has not been treated with acetylcholinesterase inhibitor (AChEI), i.e.,donepezil, galantamine, or rivastigmine, at the time of screening.

  5. The patient is able to comply with the study procedures in the view of theinvestigator.

  6. Evidence of frontotemporal hypometabolism at PET imaging.

  7. Evidence of amyloid markers excluding Alzheimer's disease (cerebrospinal fluidAbeta/Tau dosages or amyloid PET imaging).

  8. Signature and date of written ICF prior to entering in the study

  9. Female patient must be neither pregnant nor breastfeeding. Women of childbearingpotential should be willing to use contraception while receiving Rotigotine and forsix months after its last assumption

Exclusion

Exclusion Criteria:

  1. Significant neurodegenerative disorder of the central nervous system other than FTDe.g., Alzheimer's disease, Lewy body dementia, Parkinson's disease, multiplesclerosis, progressive supranuclear palsy, normal pressure hydrocephalus,Huntington's disease, any condition directly or indirectly caused by TransmissibleSpongiform Encephalopathy (TSE), Creutzfeldt-Jakob Disease (CJD), variantCreutzfeldt-Jakob Disease (vCJD), or new variant Creutzfeldt-Jakob Disease (nvCJD)

  2. Significant intracranial focal or vascular pathology seen on brain MRI scan within amaximum of 6 months before Baseline leading to a diagnosis other than probable FTD.

  3. The patients has history of seizure (with the exception of febrile seizures inchildhood).

  4. Metal implants in the head (except dental), pacemaker, cochlear implants, or anyother non-removable items that are contraindications to MR imaging.

  5. Treatment currently or within 3 months before Baseline with any of the followingmedications: Typical and Atypical antipsychotics (i.e., Clozapine, Olanzapine);Antiepileptics drugs (i.e., Carbamazepine, Primidone, Pregabalin, Gabapentin);Antidepressants (i.e., Citalopram, Duolxetine, Paroxetine).

Study Design

Total Participants: 75
Treatment Group(s): 3
Primary Treatment: Placebo
Phase: 2
Study Start date:
June 03, 2021
Estimated Completion Date:
April 01, 2024

Study Description

The current study has the ambition to provide the first-time evidence of the clinical impact, at cognitive and behavioral level, of a dopamine-based treatment in newly diagnosed bvFTD patients.

To evaluate the cognitive and behavioral effects of RTG administration, the investigators will employ a battery of tests assessing global cognition, executive functions, language and behavior.

The battery will include: Neuropsychiatric Inventory (NPI) and Frontal Behavioral Inventory (FBI) to evaluate behavior, Clinical Dementia Rating Scale-Frontotemporal Dementia Sum Of Boxes (CDR-FTD SOB) to evaluate global disease severity, Frontal Assessment Battery (FAB) to evaluate frontal functions, Screening for aphasia in Neurodegeneration (SAND) to evaluate language functions, Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) to evaluate activities of daily living, the Addenbrooke's Cognitive Examination Revised (ACE-R) to evaluate global cognition.

To evaluate changes in brain metabolism the investigators will perform 2 FDG-PET scans before starting the treatment and at the end of week 24.

Neurophysiological investigations will be performed to identify quantifiable biomarkers underlying the effects induced by dopamine agonist on the bvFTD brain. In particular, the investigators will use multimodal neurophysiological tools based on TMS-EMG and TMS-EEG. More specifically, different paired-pulse TMS protocols will be used to evaluate in vivo the activity of different intracortical circuits, such as short intracortical inhibition (SICI), reflecting GABA(A)-ergic neurotransmission; long intracortical inhibition (LICI), evaluating GABA(B)-ergic neurotransmission; short afferent inhibition (SAI) evaluating cholinergic neurotransmission and intermittent theta burst stimulation (iTBS) probing cortical plasticity mechanisms, such as long- term potentiation (LTP). The effects of these protocols will be evaluated by means of motor-evoked potentials, recordable with EMG. TMS-EEG will be used to measure the effects of RTG on frontal and parieto-temporal cortical activity, in terms of cortical excitability, oscillatory activity and connectivity. The investigators will evaluate the effects of the DA drug on brain activity and plasticity by analyzing MEPs and TEPs before and after the treatment. The investigators expect to find modulations in the high EEG frequencies (beta and gamma oscillatory activities) and/or in the indexes of cortical reactivity and plasticity (amplitude of TEPs and MEPs) that correlate with improvement in clinical assessment.

Connect with a study center

  • Giacomo Koch

    Rome, <None> 00179
    Italy

    Site Not Available

  • Department of Neurology, University of Brescia

    Brescia,
    Italy

    Site Not Available

  • Santa Lucia Foundation

    Rome, 00179
    Italy

    Site Not Available

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