Evaluation of the Role of the Noradrenergic System in Pain Perception in Parkinson's Disease (DOULOX)

Patients suffering from Parkinson's disease (PD) frequently experienced painful sensations that could be, in part, due to a central modification of nociception mechanisms. Previous studies have shown that pain perception was altered in Parkinson's disease (subjective and objective pain thresholds and pain-induced cerebral activity) and that administration of L-Dopa normalized this alteration. In the central nervous system, L-Dopa is converted in dopamine and in norepinephrine. Apomorphine (a dopamine agonist) has no effect on pain threshold and pain-induced cerebral activity. Therefore the noradrenergic system could be involved in pain alteration in PD.

To assess the role of noradrenergic system in pain in patients with PD, we chose duloxetine (norepinephrine and serotonin reuptake inhibitor)because a recent study had shown that duloxetine allowed an improvement of pain clinical scores (pain questionnaires) in patients with PD.

36 patients will be enrolled in this study. We supposed that a chronic intake of duloxetine increase the pain perception level compare to the placebo. This increase would be the same than those observed with L-Dopa.

Study Overview

• Status: Completed
• Conditions: Parkinson's Disease
• Intervention / Treatment: Drug: duloxetine; Drug: injection of apomorphine; Drug: injection of placebo of L-Dopa; Drug: placebo of duloxetine; Drug: injection of placebo of apomorphine; Drug: L-Dopa

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Toulouse, France, 31059
    • CIC, Purpan Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with clinical diagnosis of Parkinson's disease according to the criteria of the UKPDSBB
• Parkinson's disease patients with a score ≤ 3 on the Hoehn and Yahr scale
• Patients treated with dopaminergic antiparkinsonian drugs (L-Dopa, dopamine agonists, ICOMT…)
• Patients affiliated to a social protection program
• Women with efficacy contraception

Exclusion Criteria:

• Patients suffering from another pathology causing chronic pain (rheumatic disease, traumatic or orthopedic pathologies…)
• Parkinson's disease patients with a score > 3 on the Hoehn and Yahr scale
• Depressed patients (MADRS score < 16)
• Patients suffering from a cancer
• Patients under tutelage, curatella or law protection
• Patients with a complete contraindication against apomorphine injections or duloxetine administration (selective serotonin reuptake inhibitor and monoamine oxydase inhibitors)
• Patients without any control of their arterial hypertension
• Patients with a neuroleptic treatment
• Pregnant women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: duloxetine; The first group (12 patients) will receive, after 28 days of duloxetine treatment, one duloxetine dose, an injection of apomorphine and a placebo of L-Dopa.	Drug: duloxetine; administration during 28 days; Drug: injection of apomorphine; injection performed at D28; Drug: injection of placebo of L-Dopa; performed at D28
Placebo Comparator: positive control (L-Dopa); The second group (12 patients) will receive, after 28 days of placebo treatment, one placebo dose of duloxetine, an injection of apomorphine and injection of placebo of L-Dopa.	Drug: injection of apomorphine; injection performed at D28; Drug: injection of placebo of L-Dopa; performed at D28; Drug: placebo of duloxetine; administration during 28 days
Placebo Comparator: negative control; The third group will receive, after 28 days of placebo treatment, one placebo of duloxetine, an injection of placebo of apomorphine and a dose of L-Dopa.	Drug: placebo of duloxetine; administration during 28 days; Drug: injection of placebo of apomorphine; performed at D28; Drug: L-Dopa; performed at D28; Other Names: injection of L-dopa

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subjective pain threshold determined using thermal stimulations (thermotest) with the method of levels	Before duloxetine intake and after one month of chronic duloxetine intake	One month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective pain threshold determined recording the nociceptive reflex of flexion	Before duloxetine intake and after one month of chronic duloxetine intake	One month
Clinical evaluation of the severity of the motor handicap of patients using the Unified Parkinson's Disease Rating Scale (UPDRS III)	Before duloxetine intake and after one month of chronic duloxetine intake	One month

Collaborators and Investigators

• Sponsor: University Hospital, Toulouse
• Collaborators: French Parkinson Association
• Investigators: Principal Investigator: Christine Brefel-Courbon, MD, Purpan hospital, Toulouse

Study record dates

Study Major Dates

• Study Start: May 1, 2011
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: December 30, 2011
• First Submitted That Met QC Criteria: January 2, 2012
• First Posted (Estimate): January 5, 2012

Study Record Updates

• Last Update Posted (Actual): February 23, 2017
• Last Update Submitted That Met QC Criteria: February 21, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: Noradrenergic system and pain in Parkinson's disease
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Gastrointestinal Agents; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Antidepressive Agents; Dopamine Agonists; Dopamine Agents; Serotonin and Noradrenaline Reuptake Inhibitors; Emetics; Antiparkinson Agents; Anti-Dyskinesia Agents; Duloxetine Hydrochloride; Apomorphine; Levodopa; Dihydroxyphenylalanine
• Other Study ID Numbers: 09 303 03

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided