Palliative care in Parkinson's Disease
PI: Angelo Antonini
Parkinson’s Disease (PD) is the second most common neurodegenerative disorder and is characterized in its advanced stages by motor and non-motor complications causing progressive loss of autonomy in activities of daily living, poor quality of life, marked caregiver distress, and high utilization of medical services. Similar to cancer patients, albeit for much longer duration, PD patients have considerable (and mounting) unmet physical, psychosocial and spiritual needs, and experience great problems with continuity of care. The overall ambition of PD_Pal is to validate a new model of palliative care which would be easily integrated with traditional management when disability limits mobility and independence. PD_Pal will provide an added layer of support to patients, their loved ones, and treating clinicians. PD_Pal randomised controlled trial will provide evidence on the effectiveness of specialized, multidisciplinary, outpatient palliative care intervention (Advance Care Planning) in improving family satisfaction, symptom management and quality of life. PD_Pal will also further prove the feasibility and economic sustainability of this approach by the active involvement of patients lay associations as well relevant medical societies. PD_Pal team includes leading experts in both neurology and palliative care with key-roles in both national and international PD working groups. PD_Pal will develop a new set of evidence-based Guidelines and a Massive Online Course (MOOC) for Palliative Care in PD involving in the process experts from the European Association for Palliative Care, the European Academy of Neurology and the Movement Disorders Society. Thus, PD_Pal is best positioned to transfer this knowledge to all European countries and ensure that “PD_Pal Guidelines” will translate into best practice. The PD_Pal MOOC “Best Care for People with Late Stage Parkinson” will be integrated into the WHO supported interdisciplinary post-graduate palliative care curriculum.
Sito web: www.pdpal.eu

Integrated Parkinson Care Networks: addressing complex care in Parkinson disease in contemporary society
Local Investigator: Angelo Antonini
PI: Thiago Mestre
In the European Union, the cost and burden of brain disease are overwhelming (€800 billion/year). Parkinson disease (PD) is a non-curable neurodegenerative disease with complex motor and non-motor care needs. PD is one of the top 10 most costly brain disorders in EU, and its incidence is expected to double by 2030. The need for services will increase and consequently the burden for healthcare systems. How can we address complex care delivery in a manner that is cost-effective and sustainable NOW?
Multispecialty care is an attractive care delivery model, but past designs failed to be effective or sustainable in PD. Partners in iCARE-PD have started to develop innovative sustainable care models shifting from “(in)outpatient care” to “home-based and integrated health care” that focus in Integrated Care, Self-management support and Technology-enabled Care using a patient-centred approach. We hypothesize that this set of interventions can play a critical role in a solution to the challenges of complex care in PD, enhancing patient dignity and care equity. For the success of this care model in a varied social/economic landscape, we aim to:
1. Determine WHAT and HOW Integrated Care and SMS can be implemented across different social contexts;
2. To develop patient-centred digital health technology T to optimize complex care delivery in PD
3. To develop novel holistic measures of care with social meaning;
4. Test the feasibility of the resulting patient-centred multi-national integrated care delivery model.
iCARE-PD was built based on social and cultural diversity of its partners, with secured access to existing national research networks and patient associations. iCARE-PD is made of a wide multidisciplinary team of internationally-recognized PD researchers, social scientists, health geographers, health economists, engineers, computer scientists, experts in law/ethics, patient-centred design, and complex interventions. The success and gained experience in iCARE-PD will be transferable to other neurodegenerative disorders.

INnovative products with high biotechnological content for BIOMEDICAL sector
PI: Angelo Antonini
The project has different objectives. In cooperation with the Department of Biology, our research group aims to create biotechnological systems and innovative products for the treatment of chronic diseases and aging pathologies.
During the project, therapeutic devices for treating chronic diseases, and innovative and biotechnological systems for treating aging pathologies will be developed together with in vitro verification of the biological properties of the produced systems and products.
Partners: Università del Sannio, Università della Basilicata

Multicenter study to validate the mild cognitive impairment in Italian patients with Parkinson’s Disease
PI: Roberta Biundo
IRCCS Ospedale San Camillo Foundation, Venezia Lido
The cognitive impairments associated with Parkinson’s Diseases (PD) are common and affect the patients quality of life. The attention of the scientific community for PD patients with mild cognitive impairment (PD MCI) is increasing, as it is considered as a transition between the normal cognitive status and dementia (PDD). An important milestone in this process was the definition of the clinical criteria for the PD-MCI diagnosis. Using those criteria, PD-MCI can be frequently diagnosed even on de-novo (non-treated) patients and is characterized by a heterogeneous cerebral morphology. Moreover, with the most sensitive tests it is possible to discriminate between different cognitive status or identify a cognitive fall over time, mainly linked to dementia. However, the criteria for PD-MCI diagnosis published by the International Movement Disorders Society (MDS) do not provide: i) the most appropriate set of neurophysiological tests to unveil cognitive deficits and deterioration over time; ii) the thresholds to classify the pathological performance (-2SD, -1.5SD or 1SD under the normal values), and iii) the Italian regulations to define each test contribution to identify the individual cognitive status. These criticalities highlight the need of validating the MDS criteria for the clinical practice of the PD-MCI diagnosis, allowing for the results comparison among studies. The study-group for the international validation of the MDS PD-MCI criteria confirmed their high potential as a dementia marker for second level PD-MCI patients. These data have been used to preliminary identify the tests sensitive to the cognitive deterioration in PD patients. However, systematic studies to deal with the described criticalities are needed.
The objective of this project are:
1) to identify the thresholds to classify the pathological performance (-2SD, -1.5SD or 1SD under the normal values) to minimize the false positive detection of PD-MCI status;
2) to create a database with Italian normative data to improve the structural validity of each test and to measure the real contribution of each test to identify the individual cognitive impairment, minimizing both the Type-I and Type-II errors; 3) to identify a sub-sample of neurophysiological tests to identify the mild cognitive damage in PD patients, and that can be also used to monitor the cognitive profile during the clinical trial.

Studio di fase IIB, randomizzato, in doppio cieco, controllato con placebo e multicentrico per valutare l’efficacia e la sicurezza di prasinezumab per via endovenosa in partecipanti con malattia di Parkinson in fase iniziale.
PI: Angelo Antonini
Obiettivo primario: L’obiettivo primario di efficacia dello studio consiste nel valutare l’efficacia di prasinezumab rispetto al placebo in base al seguente endpoint: Tempo alla progressione significativa dei segni motori della malattia, valutato come un aumento; 5 punti del punteggio ottenuto nella Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Parte III, rispetto al basale.

Studio di fase 2A, randomizzato, in doppio cieco, controllato con placebo, della durata di 18 mesi, per valutare l’efficacia, la sicurezza, la tollerabilità e la farmacocinetica di UCB0599 somministrato per via orale nei partecipanti allo studio con malattia di Parkinson allo stadio iniziale.
PI: Angelo Antonini
Obiettivo primario: Punteggio totale secondo la scala unificata di valutazione della malattia di Parkinson della Società per i disturbi del movimento (Movement Disorder Society-Unified Parkinson’s Disease Rating Scale, MDS-UPDRS) Parti IIII (periodo: dal Basale a 18 mesi).

Uno studio di Fase IIB randomizzato, in doppio cieco, controllato con placebo, che valuta l'efficacia del mesdopetam durante il tempo ON giornaliero senza fastidiose discinesie in pazienti con malattia di Parkinson.
PI: Angelo Antonini
Obiettivo primario: Valutare l'efficacia del trattamento aggiuntivo con mesdopetam dosato a 2,5 mg, 5 mg o 7,5 mg b.i.d. (che consente una singola riduzione della dose di 2,5 mg a una dose minima di 2,5 mg, fino al giorno 28) rispetto al placebo in pazienti con PD che presentano discinesia fastidiosa in fase ON.

Studio clinico randomizzato in doppio cieco, controllato con placebo per valutare l’effetto di opicapone 50 mg in pazienti affetti da malattia di Parkinson con fluttuazioni motorie di fine dose e dolore associato
PI: Angelo Antonini
Obiettivo primario: Studiare l'efficacia di opicapone 50 mg quando somministrato con il trattamento esistente a base di Levodopa più un inibitore della dopa decarbossilasi, in pazienti affetti da malattie di Parkinson con fluttuazioni motorie di fine dose e dolore associato.

Un'estensione in aperto dello Studio M15-741 per valutare la sicurezza e la tollerabilità dell'esposizione giornaliera per 24 ore all'infusione sottocutanea continua di ABBV-951 in soggetti con malattia di Parkinson.
PI: Angelo Antonini
Numero centri coinvolti: 7.
clinicaltrial.gov link: clicca qui.

Studio pilota, di 12 settimane, multicentrico, randomizzato, in doppio cieco, controllato con placebo, esplorativo, per valutare la sicurezza e l'efficacia di safinamide 200 mg una volta algiorno, come terapia aggiuntiva, in pazienti con possibile o probabile variante parkinsoniana dell'atrofia multisistemica
PI: Angelo Antonini
clinicaltrial.gov link: non disponibile.

Studio clinico randomizzato controllato per paragonare la sicurezza e l'efficacia del IPX203 a rilascio-immediato di Carbidopa-Levodopa in pazienti con Malattia di Parkinson con fluttuazioni motorie.
PI: Angelo Antonini
clinicaltrial.gov link: non disponibile.

A multicenter, randomized, active-controlled, double-blind, double-dummy, parallel group clinical trial, investigating the efficacy, safety, and tolerability of continuous subcutaneous ND0612 infusion in comparison to oral IR-LD/CD in subjects with Parkinson’s disease experiencing motor fluctuations (BouNDless).
PI: Angelo Antonini
Primary objective: to determine the effect of ND0612 on daily “ON” time without troublesome dyskinesia (defined as the sum of "ON" time without dyskinesia and “ON” time with non-troublesome dyskinesia) using subject-completed “ON/OFF” diary assessments of motor function in subjects with Parkinson’s disease (PD) experiencing motor fluctuations.
clinicaltrial.gov link: https://clinicaltrials.gov/ct2/show/NCT04006210

CVL-751-PD-001 A phase 3, double-blinded, randomized, placebo-controlled, parallel-group, 27-week trial of the efficacy, safety, and tolerability of two fixed doses of Tavapadon in early Parkinson's Disease.
CVL-751-PD-003 A phase 3, double-blinded, randomized, placebo-controlled, parallel-group, flexible-dose, 27-week trial of the efficacy, safety, and tolerability of Tavapadon as Adjunctive Therapy for Parkinson's Disease in Levodopa-Treated adults with motor fluctuations.
CVL-751-PD-004 58-week open-label trial of Tavapadon in Parkinson's Disease.
PI: Angelo Antonini
Primary objective:
CVL-751-PD-001 to assess the efficacy of 2 fixed doses of Tavapadon in subjects with early PD;
CVL-751-PD-003 to assess the effect of Tavapadon on the change from baseline in total daily hours of “on” time without troublesome dyskinesia in levodopa (L-Dopa)-treated subjects with PD who are experiencing motor fluctuations;
CVL-751-PD-004 to evaluate the safety and tolerability of long-term administration of Tavapadon in subjects with PD; to evaluate the effects of Tavapadon on PD symptoms during long-term treatment; and to evaluate speech and facial expression characteristics of subjects with PD.
clinicaltrial.gov link: not available.

Uno studio in doppio cieco, controllato con placebo, fase 2 per valutare l'efficacia, la tollerabilità dell'UCB0107 in soggetti con Paralisi Progressiva Supranucleare (PSP).
PI: Angelo Antonini
Obiettivo primario: valutare l'efficacia dell'UCB0107 nel rallentare la progressione della malattia in soggetti con PSP misurato dal punteggio totale della scala di valutazione PSP (PSPRS).
clinicaltrial.gov link: non disponibile.

CTH-301 An Open-Label, Phase 3 Study Examining the Long-Term Safety, Tolerability and Efficacy of APL-130277 in Levodopa Responsive Patients with Parkinson’s Disease Complicated by Motor Fluctuations (“OFF” Episodes)
CTH-302 An open-label, randomized, crossover trial utilizing a single-blinded rater to evaluate APL-130277 compared to s.c. Apomorphine in Levodopa responsive subjects with Parkinson's Disease complicated by motor fluctuations.
PI: Angelo Antonini
Primary objective:
l'obiettivo principale è dimostrare l'efficacia dell'apomorfina sublinguale (sl) APL-130277 rispetto all'apomorfina sottocutanea (sc) come trattamento degli episodi "OFF" in soggetti con malattia di Parkinson (PD) misurata dal cambiamento da pre- dose fino a 90 minuti dopo la dose nel punteggio della scala di valutazione della malattia di Parkinson unificata (MDS-UPDRS) della Movement Disorder Society.
clinicaltrial.gov link: not available.

mHealth platform for Parkinson's disease
PI: Angelo Antonini
Parkinson’s is a complicated, individual disorder that many patients live with for many years/decades. For this reason, a multidisciplinary disease management, involving several professions working together (neurologists, physiotherapists, speech and language therapists, occupational therapists, dietitians), is important to ensure that the patient retains his/her independence and continues to enjoy the best quality of life possible.
The PD_manager project achieved to:
- model the behaviors of intended users of PD_manager (patients, caregivers, neurologists and other health-care providers)
- educate patients, caregivers and healthcare providers with the focus on occupational and speech therapies
- propose a set of unobtrusive, simple-in-use, co-operative, mobile devices that will be used for symptoms monitoring and collection of adherence data (smartphone, sensor insole, smart pillbox, wristband with several sensors for acceleration, heart rate, etc.).
Sito web: www.parkinson-manager.eu

Studio in doppio cieco controllato con placebo di primavanserina sulla prevenzione delle recidive per il trattamento di allucinazioni e manie associate a psicosi correlata alla demenza
PI: Angelo Antonini
Obiettivo primario: valutare la prevenzione della recidiva nei soggetti affetti da psicosi correlata a demenza e trattati con primavanserina, in confronto al placebo.
Numero centri coinvolti: 117.
clinicaltrial.gov link: clicca qui.

Uno studio randomizzato, controllato con placebo, in doppio cieco, a gruppi paralleli per valutare l'efficacia, la sicurezza e la tollerabilità di E2027 in soggetti affetti da demenza a corpi di Lewy.
PI: Angelo Antonini
Obiettivo primario: Lo scopo principale di questo studio è scoprire l'efficacia di un nuovo farmaco, chiamato E2027, in persone affette da DLB. Le persone affette da DLB presentano un deterioramento della funzione cognitiva. Potrebbero, inoltre, manifestare altri sintomiche inficiano la loro mobilità e il loro stato mentale.
Numero centri coinvolti: 80.
clinicaltrial.gov link: clicca qui.

Percorso terapeutico nella Malattia di Parkinson con fluttuazioni: studio multicentrico osservazionale italiano, PD-PAMELA.
PI: Angelo Antonini
Obiettivo primario: descrizione del percorso terapeutico associato al trattamento delle fluttuazioni in pazienti con diagnosi di MP da 10-15 anni in Italia.
clinicaltrial.gov link: non disponibile.

Studio randomizzato, in doppio cieco, controllato con placebo, a gruppi paralleli per valutare l'efficacia and la sicurezza del BHV-3241 in soggetti con Atrofia Multisistemica (M-STAR Study).
PI: Angelo Antonini
Obiettivo primario: valutare l'efficacia del BHV-3241, rispetto al placebo, misurato come cambiamento rispetto alla baseline mediante scala Unified MSA Rating Scale (UMSARS) parte I e II dopo 48 settimane e verificarne la tollerabilità in soggetti con MSA.
clinicaltrial.gov link: clicca qui.