Clinical trial NCT02864004: Apomorphine Pump in Early Stage of Parkinson's Disease (EARLY-PUMP)
Official title: Apomorphine Pump in Early Stage of Parkinson's Disease
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Parkinson's Disease
Keywords: Parkinson disease
Quality of Life
Apomorphine infusion
Lead sponsor: Rennes University Hospital
Sponsor class: OTHER
First posted: 2016-08-11
Enrollment: 134
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: 12 months
Secondary outcomes:
measure: Change in the Patient Global Impression of Change (PGIC)
timeFrame: 12 months
measure: Change in the Neurologist Global Impression of change (CGI-I)
timeFrame: 12 months
measure: 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
timeFrame: 12 months
measure: 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
timeFrame: 12 months
measure: Change in motor examination during "on" periods (MDS-UPDRS III) between the baseline assessment and the assessment at 12 months' follow up
timeFrame: 12 months
measure: Change in motor complications with MDS-UPDRS IV between the baseline assessment and the assessment at 12 months' follow up
timeFrame: 12 months
measure: Change in number of hours per day in the "best ON" state between the baseline assessment and the assessment at 12 months' follow up
timeFrame: 12 months
measure: Change in number of hours per day in "ON" with dyskinesia between the baseline assessment and the assessment at 12 months' follow up
timeFrame: 12 months
measure: Change in number of hours per day in "OFF" state between the baseline assessment and the assessment at 12 months' follow up
timeFrame: 12 months
measure: Change in number of Sleeping-hours per day between the baseline assessment and the assessment at 12 months' follow up
timeFrame: 12 months
measure: Change in Score of the Non-Motor Symptoms Scales (NMSS) for PD between the baseline assessment and the assessment at 12 months' follow up
timeFrame: 12 months
measure: Change in psychosocial functioning PD (SCOPA-PS) between the baseline assessment and the assessment at 12 months' follow up
timeFrame: 12 months
measure: Changes in score of depressive symptoms (BDI) between the baseline assessment and the assessment at 12 months' follow up
timeFrame: 12 months
measure: Change in occurrence of anxiety (STAI-S) between the baseline assessment and the assessment at 12 months' follow up
timeFrame: 12 months
measure: Change in pain assessed on the Visual Analog Scale (VAS) between the baseline assessment and the assessment at 12 months' follow up
timeFrame: 12 months
measure: Change in cognitive function between the baseline assessment and the assessment at 12 months' follow up
timeFrame: 12 months
measure: Change in apathy assessed on the Apathy Scale between the baseline assessment and the assessment at 12 months' follow up
timeFrame: 12 months
measure: 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
timeFrame: 12 months
measure: Change of dose for treatments assessed by levodopa (L-DOPA) equivalents between the baseline assessment and the assessment at 12 months' follow up
timeFrame: 12 months
measure: Change in behavioral symptoms assessed by Ardouin Scale between the baseline assessment and the assessment at 12 months' follow up
timeFrame: 12 months
measure: Frequency, type and severity of therapy-related adverse events
timeFrame: 12 months
measure: Skin changes assessed by a clinical exam
timeFrame: 12 months
measure: Full blood count
timeFrame: 12 months
measure: Epworth Sleepiness Scale
timeFrame: 12 months
measure: Incremental Cost-Effectiveness Ratio (ICER)
timeFrame: 24 months
Other outcomes:
Locations:
city: Amiens
country: France
facility: Amiens University Hospital
city: Bayonne
country: France
facility: Bayonne Côte Basque Hospital
city: Bordeaux
country: France
facility: Pellegrin University Hospital
city: Bron
country: France
facility: Pierre Wertheimer Hospital
city: Caen
country: France
facility: Caen University Hospital
city: Clermont-Ferrand
country: France
facility: Clermont-Ferrand University Hospital
city: Lille
country: France
facility: Lille University Hospital
city: Marseille
country: France
facility: APHM, hospital of Timone
city: Montpellier
country: France
facility: Clinique Beau-Soleil
city: Montpellier
country: France
facility: Montpellier University Hospital
city: Nancy
country: France
facility: Nancy University Hospital
city: Nantes
country: France
facility: Laennec Hospital
city: Nice
country: France
facility: Pasteur 2 University Hospital
city: Nîmes
country: France
facility: Caremeau University Hospital
city: Paris
country: France
facility: Pitié-Salpêtriere Hospital
city: Poitiers
country: France
facility: Poitiers University Hospital
city: Rennes
country: France
facility: Rennes University Hospital
city: Saint- Etienne
country: France
facility: Saint-Etienne University Hospital
city: Strasbourg
country: France
facility: Hautepierre University Hospital
city: Toulouse
country: France
facility: Purpan University Hospital
Study officials:
affiliation: Rennes University Hospital
name: Sophie DRAPIER, Dr
role: PRINCIPAL_INVESTIGATOR
References: