Apomorphine Pump in Early Stage of Parkinson's Disease (EARLY-PUMP)

Parkinson's Disease Clinical Trial

— EARLY-PUMP  

Official title:

Apomorphine Pump in Early Stage of Parkinson's Disease

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02864004
• Other study ID #: 35RC15_9724_EARLY-PUMP
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: March 3, 2017
• Est. completion date: January 30, 2025

Study information

• Verified date: November 2023
• Source: Rennes University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The aim of the study is to assess the use of the apomorphine pump in earlier stages of Parkinson' Disease (PD), when motor complications have just developed and before patients are significantly affected in their social and occupational functioning. The investigators hypothesize that apomorphine pump is superior in terms of positive impact on quality of life (QoL) to oral medical therapy alone at a relatively early stage of PD, before the appearance of severe disabling motor complications thus favoring the maintain of patients' social and occupational status with a significant positive economic impact of the health system.

Description:

The recruitment period will be 36 months. The duration of the study period will be one year for each patient due to:

• adjustments of apomorphine pump parameters and oral medication (3 months interval),

• motor and psychosocial changes which need time to develop and have an impact on QoL.

At the end of the study period, two additional visits at Months 18 and 24 will be performed during an long term follow up to collect QoL and costs related data required to medico-economic analysis.

APOMORPHINE (APO) group:

The apomorphine pump will be installed and adjusted at baseline during a first hospitalization (10 days). Modifications of the hourly flow of the pump and readjustment (reduction) of anti-parkinsonian oral medication will be checked and performed at Months 1, 2, 4, 5, 6, 9 during visits and phone calls, and at month 3 during a 3 days hospitalization. Clinical evaluations will be performed at months 6 and 12.

Control group:

Patients will be treated by optimized medical treatment according to the guidelines of the European Federation of Neurological Societies. Dose adjustments will be done at Months 3, 6,

9. Clinical evaluations will be performed at months 6 and 12.

In both groups, data for medico-economic evaluation will be collected from patients at baseline, Months 6, 12, 18 and 24 for Quality Adjusted Life Year (QALYs) and costs related data from a patient's diary and French Health Insurance database.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 134
• Est. completion date: January 30, 2025
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Adults aged = 65 years,

• Idiopathic PD (According to British Brain Bank Criteria) without any other known or suspected cause of Parkinsonism,

• Hoehn and Yahr stage = 2.5 in the best ON,

• Disease duration = 4 years,

• Presence of fluctuations and/or dyskinesias for no more than 3 years,

• One of the two following forms of impairment :

• Impairment in activities of daily living (MDS-UPDRS II>6) due to PD-symptoms despite medical treatment in the worst condition or,

• Impairment of social and occupational functioning (measured with SOFAS) due to PD-symptoms despite medical treatment (51-80%),

• PDQ39 completed,

• Able to understand and remember the component of the study,

• Written informed consent,

• Patients covered with social insurance.

Exclusion Criteria:

• Dementia (MoCA < 22),

• Major uncontrolled depression at the time of assessment (BDI > 25) or Bipolar disease,

• Active hallucinations or history of hallucinations in the past year,

• Need for nursing care,

• Previous use of apomorphine pump treatment,

• History of respiratory depression,

• History of deep brain stimulation or lesional surgery for PD or intrajejunal L-Dopa,

• Presence of severe freezing or clinically relevant postural instability leading to falls during the ON state,

• Symptomatic clinically relevant and medically uncontrolled orthostatic hypotension,

• Clinically relevant hepatic dysfunction (total bilirubin >2.0 mg/dL, Alanine Amino Transferase (ALT) and Aspartate Amino Transferase (AST) >2 times the upper limit of normal),

• Clinically relevant renal dysfunction (serum creatinine >2.0 mg/dL),

• Pregnant and breastfeeding women,

• Hypersensitivity to apomorphine or any excipients of the medicinal product,

• Concomitant therapy or within 28 days prior to baseline with : alpha-methyl dopa, metoclopramide, reserpine, neuroleptics (except Clozapine), methylphenidate, or amphetamine, intrajejunal Ldopa,

• History or current drug or alcohol abuse or dependencies,

• Patients with a borderline QT interval corrected for heart rate according to Bazett's formula (QTc) of >470 ms for male and >480 ms for female at screening or history of long QT syndrome;

• Adults legally protected (under judicial protection, guardianship or supervision), persons deprived of their liberty.

Related Conditions & MeSH terms

• Parkinson Disease
• Parkinson's Disease

Intervention

Drug:
• Apomorphine
Apomorphine (5 mg/ml) is supplied as solution for infusion in a 10 ml glass ampoule Hourly flow rate is adjusted during the whole duration of the study to doses of minimum 3 mg/hour up to a maximum of 10 mg/hour

Other:
• Best Medical Treatment
Most efficient single treatment of Parkinson's disease symptoms or their combinations, in concordance with the guidelines of the European Federation of Neurological Societies

Locations

Country	Name	City	State
France	Amiens University Hospital	Amiens
France	Bayonne Côte Basque Hospital	Bayonne
France	Pellegrin University Hospital	Bordeaux
France	Pierre Wertheimer Hospital	Bron
France	Caen University Hospital	Caen
France	Clermont-Ferrand University Hospital	Clermont-Ferrand
France	Lille University Hospital	Lille
France	APHM, hospital of Timone	Marseille
France	Clinique Beau-Soleil	Montpellier
France	Montpellier University Hospital	Montpellier
France	Nancy University Hospital	Nancy
France	Laennec Hospital	Nantes
France	Pasteur 2 University Hospital	Nice
France	Caremeau University Hospital	Nîmes
France	Pitié-Salpêtriere Hospital	Paris
France	Poitiers University Hospital	Poitiers
France	Rennes University Hospital	Rennes
France	Saint-Etienne University Hospital	Saint- Etienne
France	Hautepierre University Hospital	Strasbourg
France	Purpan University Hospital	Toulouse

Sponsors (1)

Lead Sponsor	Collaborator
Rennes University Hospital

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Difference in the Parkinson's Disease Quality of Life Questionnaire (PDQ39) summary index between the baseline assessment and the assessment at 12 months' follow up		12 months
Secondary	Change in the Patient Global Impression of Change (PGIC)		12 months
Secondary	Change in the Neurologist Global Impression of change (CGI-I)		12 months
Secondary	Change in non-motor aspects of experiences of daily living (MDS-UPDRS I) between the baseline assessment and the assessment at 12 months' follow up		12 months
Secondary	Change in motor aspects of experiences of daily in "on" and "off" medication (MDS-UPDRS II) between the baseline assessment and the assessment at 12 months' follow up		12 months
Secondary	Change in motor examination during "on" periods (MDS-UPDRS III) between the baseline assessment and the assessment at 12 months' follow up		12 months
Secondary	Change in motor complications with MDS-UPDRS IV between the baseline assessment and the assessment at 12 months' follow up		12 months
Secondary	Change in number of hours per day in the "best ON" state between the baseline assessment and the assessment at 12 months' follow up		12 months
Secondary	Change in number of hours per day in "ON" with dyskinesia between the baseline assessment and the assessment at 12 months' follow up		12 months
Secondary	Change in number of hours per day in "OFF" state between the baseline assessment and the assessment at 12 months' follow up		12 months
Secondary	Change in number of Sleeping-hours per day between the baseline assessment and the assessment at 12 months' follow up		12 months
Secondary	Change in Score of the Non-Motor Symptoms Scales (NMSS) for PD between the baseline assessment and the assessment at 12 months' follow up		12 months
Secondary	Change in psychosocial functioning PD (SCOPA-PS) between the baseline assessment and the assessment at 12 months' follow up		12 months
Secondary	Changes in score of depressive symptoms (BDI) between the baseline assessment and the assessment at 12 months' follow up		12 months
Secondary	Change in occurrence of anxiety (STAI-S) between the baseline assessment and the assessment at 12 months' follow up		12 months
Secondary	Change in pain assessed on the Visual Analog Scale (VAS) between the baseline assessment and the assessment at 12 months' follow up		12 months
Secondary	Change in cognitive function between the baseline assessment and the assessment at 12 months' follow up	Change in cognitive function assessed by the Neuroscience Parkinson network's (NS-PARK) battery test	12 months
Secondary	Change in apathy assessed on the Apathy Scale between the baseline assessment and the assessment at 12 months' follow up		12 months
Secondary	Change in apathy assessed on the short version of Lille Apathy Rating Scale (LARS) between the baseline assessment and the assessment at 12 months' follow up		12 months
Secondary	Change of dose for treatments assessed by levodopa (L-DOPA) equivalents between the baseline assessment and the assessment at 12 months' follow up		12 months
Secondary	Change in behavioral symptoms assessed by Ardouin Scale between the baseline assessment and the assessment at 12 months' follow up		12 months
Secondary	Frequency, type and severity of therapy-related adverse events		12 months
Secondary	Skin changes assessed by a clinical exam		12 months
Secondary	Full blood count		12 months
Secondary	Epworth Sleepiness Scale		12 months
Secondary	Incremental Cost-Effectiveness Ratio (ICER)		24 months