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| Name | Class |
|---|---|
| Alzheimer's Drug Discovery Foundation | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Rotigotine 4 mg | Experimental | Rotigotine 4 mg/24 hours transdermal patch administration |
|
| Rotigotine 6 mg | Experimental | Rotigotine 6 mg/24 hours transdermal patch administration |
|
| Placebo | Placebo Comparator | Placebo transdermal patch administration |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Rotigotine 4Mg/24Hrs Patch | Drug | Rotigotine 4 mg/24Hrs administration for 24 weeks |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Neuropsychiatric Inventory (NPI) scale | Battery to assess behavioral changes. The scores range from 0-144 with a higher score meaning more severe behavioural disturbances. | 24 weeks |
| Frontal Behavioural Inventory (FBI) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| 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 |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Giacomo Koch | Rome | <None> | 00179 | Italy | ||
| Department of Neurology, University of Brescia |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40809903 | Derived | 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. |
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| Rotigotine 6Mg/24Hrs Patch | Drug | Rotigotine 6 mg/24Hrs administration for 24 weeks |
|
|
| Placebo | Drug | Placebo administration for 24 weeks |
|
Battery to assess behavioral changes. The scores range from 0-72 with a higher score meaning more severe behavioural disturbances.
| 24 weeks |
| Clinical Dementia Rating scale-Frontotemporal dementia Sum Of Boxes (CDR-FTDSOB) | Battery to evaluate global disease severity. The scores range from 0-24 with a higher score meaning higher disease severity. | 24 weeks |
| Screening for aphasia in Neurodegeneration (SAND) scale | Battery to evaluate language functions. The scores range from 0-84 with a higher score meaning less severe language deficits. | 24 weeks |
| Mini Mental State Examination (MMSE) | battery to evaluate global cognition. The scores range from 0-30 with a higher score meaning less cognitive impairment. | 24 weeks |
| Addenbrooke's Cognitive Examination Revised (ACE-R) | battery to evaluate global cognition. The scores range from 0-100 with a higher score meaning less cognitive impairment. | 24 weeks |
| Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) | battery to evaluate activities of daily living. The scores range from 0-78 with lower scores indicating more severe functional impairment. | 24 weeks |
| CGIC questionnaire | questionnaire to evaluate clinically meaningful change | 24 weeks |
| 18F-FDG CT/PET | Change in brain glucose metabolism will be measured via FDG-PET | 24 weeks |
| Long intracortical inhibition (LICI) | TMS protocol to evaluate GABA(B)ergic transmission | 24 weeks |
| Short intracortical inhibition (SICI) | TMS protocol to evaluate GABA(B)ergic transmission | 24 weeks |
| Short-Latency Afferent Inhibition (SAI) | TMS protocol to evaluate cholinergic transmission | 24 weeks |
| Intermittent Theta Burst Stimulation (iTBS) | TMS protocol to evaluate cortical plasticity | 24 weeks |
| TMS-EEG | power in beta-gamma band to evaluate prefrontal cortical oscillatory activity | 24 weeks |
| Nature, frequency and severity of adverse events (AEs) | To assess the safety and tolerability | 24 weeks |
| Brescia |
| Italy |
| Santa Lucia Foundation | Rome | 00179 | Italy |
| ID | Term |
|---|---|
| D057180 | Frontotemporal Dementia |
| D003704 | Dementia |
| D018888 | Aphasia, Primary Progressive |
| D020774 | Pick Disease of the Brain |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| D019636 | Neurodegenerative Diseases |
| D057174 | Frontotemporal Lobar Degeneration |
| D057177 | TDP-43 Proteinopathies |
| D057165 | Proteostasis Deficiencies |
| D008659 | Metabolic Diseases |
| D001037 | Aphasia |
| D013064 | Speech Disorders |
| D007806 | Language Disorders |
| D003147 | Communication Disorders |
| D019954 | Neurobehavioral Manifestations |
| D009461 | Neurologic Manifestations |
| ID | Term |
|---|---|
| D009750 | Nutritional and Metabolic Diseases |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D065886 | Neurodevelopmental Disorders |
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| ID | Term |
|---|---|
| C047508 | rotigotine |
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