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

NCT01504178 | Completed Phase 3

• 1 other identifier: 09 303 03
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Parkinson's Disease

Keywords

Noradrenergic system and pain in Parkinson's disease

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Objective pain threshold determined recording the nociceptive reflex of flexion

  One month

• Clinical evaluation of the severity of the motor handicap of patients using the Unified Parkinson's Disease Rating Scale (UPDRS III)

  One month

Study Arms (3)

duloxetine

EXPERIMENTAL

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; Drug: injection of apomorphine; Drug: injection of placebo of L-Dopa

positive control (L-Dopa)

PLACEBO COMPARATOR

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: placebo of duloxetine; Drug: injection of apomorphine; Drug: injection of placebo of L-Dopa

negative control

PLACEBO COMPARATOR

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; Drug: injection of placebo of apomorphine; Drug: L-Dopa

Interventions

duloxetine DRUG

administration during 28 days

duloxetine

placebo of duloxetine DRUG

administration during 28 days

negative control; positive control (L-Dopa)

injection of apomorphine DRUG

injection performed at D28

duloxetine; positive control (L-Dopa)

injection of placebo of apomorphine DRUG

performed at D28

negative control

L-Dopa DRUG

performed at D28

Also known as: injection of L-dopa

negative control

injection of placebo of L-Dopa DRUG

performed at D28

duloxetine; positive control (L-Dopa)

Eligibility Criteria

• Age: 30 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Toulouse: lead
• French Parkinson Association: collaborator

Study Sites (1)

CIC, Purpan Hospital

Toulouse, 31059, France

Location

MeSH Terms

Conditions

Parkinson Disease

Interventions

Duloxetine Hydrochloride; Levodopa

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Dihydroxyphenylalanine; Catecholamines; Amines; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Tyrosine

Study Officials

• Christine Brefel-Courbon, MD

  Purpan hospital, Toulouse

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 30, 2011
• First Posted: January 5, 2012
• Study Start: May 1, 2011
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: February 23, 2017

Record last verified: 2017-02

Locations

FR (1)