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

Sponsor

University Hospital, Toulouse (Other)

Overall Status

Completed

CT.gov ID

NCT01504178

Collaborator

French Parkinson Association (Other)

Enrollment

Location

Arms

Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

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.

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

Study Design

Study Type:

Interventional

Actual Enrollment :

28 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Basic Science

Official Title:

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

Study Start Date :

May 1, 2011

Actual Primary Completion Date :

Dec 1, 2015

Actual Study Completion Date :

Dec 1, 2015

Arms and Interventions

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: 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 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

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: 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 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

Outcome Measures

Primary Outcome Measures

Subjective pain threshold determined using thermal stimulations (thermotest) with the method of levels [One month]
Before duloxetine intake and after one month of chronic duloxetine intake

Secondary Outcome Measures

Objective pain threshold determined recording the nociceptive reflex of flexion [One month]
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) [One month]
Before duloxetine intake and after one month of chronic duloxetine intake

Eligibility Criteria

Criteria

Ages Eligible for Study:

30 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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