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

Phase 3

Completed

• Conditions: Parkinson's Disease
• Interventions: Drug: placebo of duloxetine; Drug: duloxetine; Drug: injection of placebo of apomorphine; Drug: injection of apomorphine; Drug: injection of placebo of L-Dopa; Drug: L-Dopa

• Registration Number: NCT01504178
• Lead Sponsor: University Hospital, Toulouse

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2011-05
• Study First Submitted: 2011-12-30
• Study First Submitted QC: 2012-01-02
• Study First Posted: 2012-01-05
• Primary Completion: 2015-12
• Study Completion: 2015-12
• Status Verified: 2017-02
• Last Update Submitted: 2017-02-21
• Last Update Posted: 2017-02-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 28

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
negative control	injection of placebo of apomorphine	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.
positive control (L-Dopa)	placebo of duloxetine	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.
positive control (L-Dopa)	injection of placebo of 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.
negative control	placebo of duloxetine	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.
duloxetine	injection of apomorphine	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.
positive control (L-Dopa)	injection of apomorphine	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.
duloxetine	injection of placebo of L-Dopa	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.
duloxetine	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.
negative control	L-Dopa	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.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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
Objective pain threshold determined recording the nociceptive reflex of flexion	One month	Before duloxetine intake and after one month of chronic duloxetine intake

Trial Locations

Locations (1)

CIC, Purpan Hospital; 🇫🇷 Toulouse, France