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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by University Hospital, Toulouse
Sponsor:
Collaborator:
French Parkinson Association
Information provided by (Responsible Party):
University Hospital, Toulouse
ClinicalTrials.gov Identifier:
NCT01504178
First received: December 30, 2011
Last updated: June 11, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Parkinson's Disease
Drug: duloxetine
Drug: placebo of duloxetine
Drug: injection of apomorphine
Drug: injection of placebo of apomorphine
Drug: injection of L-Dopa
Drug: injection of placebo of L-Dopa
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Evaluation of the Role of the Noradrenergic System in Pain Perception in Parkinson's Disease

Resource links provided by NLM:


Further study details as provided by University Hospital, Toulouse:

Primary Outcome Measures:
  • Subjective pain threshold determined using thermal stimulations (thermotest) with the method of levels [ Time Frame: One month ] [ Designated as safety issue: Yes ]
    Before duloxetine intake and after one month of chronic duloxetine intake


Secondary Outcome Measures:
  • Objective pain threshold determined recording the nociceptive reflex of flexion [ Time Frame: One month ] [ Designated as safety issue: Yes ]
    Before duloxetine intake and after one month of chronic duloxetine intake

  • Clinical evaluation of the severity of the motor handicap of patients using the Unified Parkinson's Disease Rating Scale (UPDRS III) [ Time Frame: One month ] [ Designated as safety issue: Yes ]
    Before duloxetine intake and after one month of chronic duloxetine intake


Estimated Enrollment: 36
Study Start Date: May 2011
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 a placebo of L-Dopa.
Drug: placebo of 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: negative control
The third group will receive, after 28 days of placebo treatment, one placebo dose of duloxetine, an injection of a 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: injection of L-Dopa
performed at D28

  Eligibility

Ages Eligible for Study:   30 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 from 30 to 70 years old (male or female)
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01504178

Contacts
Contact: Christine Brefel-Courbon, MD (0) 5 61 14 59 62 ext 33 christine.brefel-courbon@univ-tlse3.fr
Contact: Claire Thalamas, MD (0)5 61 77 91 03 ext 33 thalamas@toulouse.inserm.fr

Locations
France
CIC, Purpan Hospital Recruiting
Toulouse, France, 31059
Contact: Christine Brefel-Courbon, MD    (0)5 61 14 59 62    christine.brefel-courbon@univ-tlse3.fr   
Principal Investigator: Brefel-Courbon Christine, MD         
Sponsors and Collaborators
University Hospital, Toulouse
French Parkinson Association
Investigators
Principal Investigator: Christine Brefel-Courbon, MD Purpan hospital, Toulouse
  More Information

No publications provided

Responsible Party: University Hospital, Toulouse
ClinicalTrials.gov Identifier: NCT01504178     History of Changes
Other Study ID Numbers: 09 303 03
Study First Received: December 30, 2011
Last Updated: June 11, 2014
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by University Hospital, Toulouse:
Noradrenergic system and pain in Parkinson's disease

Additional relevant MeSH terms:
Parkinson Disease
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Movement Disorders
Nervous System Diseases
Neurodegenerative Diseases
Parkinsonian Disorders
Apomorphine
Duloxetine
Levodopa
Adrenergic Agents
Adrenergic Uptake Inhibitors
Analgesics
Anti-Dyskinesia Agents
Antidepressive Agents
Antiparkinson Agents
Autonomic Agents
Central Nervous System Agents
Dopamine Agents
Dopamine Agonists
Dopamine Uptake Inhibitors
Emetics
Gastrointestinal Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Neurotransmitter Uptake Inhibitors
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 20, 2014