Clinical trial NCT05355064: Efficacy of Oral Administration of Trehalose in Patients With Parkinson Disease
Official title: Efficacy of Oral Administration of Trehalose in Patients With Parkinson Disease in Both Idiopathic and Induced by LRRK2 Mutation
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Parkinson Disease
Lead sponsor: Neuromed IRCCS
Sponsor class: OTHER
First posted: 2022-05-02
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Parkinson's disease (PD) is a neurodegenerative disease characterized by the neurodegeneration of substance nigra pars compacta (SNpc) and the formation of alpha-synuclein protein aggregates in neurons. Although most PD patients are sporadic, it is now clear that genetic factors contribute to the pathogenesis of PD. Indeed, LRRK2 G2019S mutation is one of the most common causes of familial PD. The phenotype corresponding to this mutation is a late-onset form of PD characterized by the accumulation of the N-ethylmaleimide sensitive factor (NSF) in neurons. It is due to a dysfunction of the physiological autophagy processes occurring at cellular level, mainly affecting autophagy mediated by chaperone proteins (Chaperon Mediated Autophagy, CMA), responsible for the clearance of alpha synuclein at the lysosomal level. This condition, although sensitive to treatment with L-DOPA and dopamine agonists, does not currently have any specific therapy.

Recently, in a mouse model carrying the LRRK2 mutation, it has been demonstrated that treatment with trehalose is able to reduce the accumulation of NSF deposits in neurons of various brain areas such as the substantia nigra, striatum, cortex and hippocampus. The reduction of protein aggregates correlates with intracellular molecules related to the activation of apoptotic processes in damaged neurons. Moreover, it has been found a significant improvement in motor and cognitive performance. The aim of the present study is to evaluate the safety and tolerability of trehalose in two groups of patients affected by idiopathic PD and PD carrying the LRRK2 mutation, respectively. Moreover, the investigators will collect preliminary data on the effect that this molecule potentially has on disease course in both groups. The treatment duration will be 24 weeks and the overall study duration approximately 12 months. The populations observed will be composed of subjects affected by idiopathic PD and familial PD carrying the genetically confirmed LRRK2 mutation. Enrolled subjects will daily take trehalose in oral administration. Safety will be assessed by detecting any adverse events and analyzing blood chemistry parameters. The effect of trehalose will be evaluated through periodic clinical examinations, including the administration of specific scales and questionnaires.


Eligibility criteria: Inclusion Criteria:

* Ability to provide written informed consent;
* PD diagnosis according to UK Parkinson's Disease Society Brain Bank Clinical Diagnostic Criteria (UKPDS);
* Age between 18 and 80 years (inclusive);
* Hoehn \& Yahr staging \> 1;

Exclusion Criteria:

* Inability to provide written informed consent;
* Diagnosis of other concomitant neurodegenerative disease;
* Concomitant treatment with drugs similar to trehalose;
* Hypersensitivity or intolerance to the active substance administered;
* Severe swallowing problems;
* Participation in other interventional studies within 30 days from the screening;
* Other medical conditions that can interfere with results or endanger the participant.

Primary outcomes:
measure: Clinical laboratory test results at each visit from baseline to follow-up period
timeFrame: 1-36 weeks
measure: 1. Physical and neurological examination findings, at each visit.
timeFrame: 1-36 weeks
Secondary outcomes:
measure: Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS)
timeFrame: 1-36 weeks
measure: Assessment of General Cognitive Functioning on the Mini Mental State Examination (MMSE)
timeFrame: 1- 36 weeks
measure: The differences between the MoCa test score from baseline to follow up period
timeFrame: 1-36 weeks
measure: Changes from baseline in the Quality of Life in Neurological Disorders ( NeuroQol) and EQ-5D-5L questionnaires
timeFrame: 1- 36 weeks
Other outcomes:
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