Opioidergic and Noradrenergic Systems in Central Parkisonian Pain

Official title

Role of Opioidergic and Noradrenergic Systems in Central Parkisonian Pain

Overview

The goal of this study is to evaluate the differences in functional physiopathology of the opioid and noradrenergic systems between Parkinson's patients with central pain and Parkinson's patients without central pain. Using PET-MRI data, investigators aim to observe opioids receptors availability using \[11C\]Carfentanil (µ opioid receptor agonist) and altered α2-AR density with \[11C\]Yohimbine (adrenergic α2 receptor antagonist).

Interventions

• Other PET-MRI exam with administration of [11C]Carfentanil
  Recording of functional neuroimaging data will begin immediately after intravenous injection of \[11C\]Carfentanil and will last for 51 minutes in a resting state. The dose will be 250 MBq/kg +-10 %.
• Other PET-MRI exam with administration of [11C]Yohimbine
  Recording of functional neuroimaging data will begin immediately after intravenous injection of \[11C\]Yohimbine and will last for 70 minutes in a resting state. The dose will be 370 MBq/kg +- 10 %.

Primary outcome measures

• Difference between non-displaceable binding potential of radiotracer in brain region involved in pain [Time frame: At the time of PET-MRI scan at Day 75]

Secondary outcome measures (3)

• Correlation between BPND of both tracer and pain intensity of parkinsonian patient [Time frame: At the time of PET-MRI scan at Day 75]
• Pain matrix area [Time frame: At the time of PET-MRI scan at Day 75]
• ASL measure [Time frame: At the time of PET-MRI scan at Day 75]

Eligibility criteria

Inclusion criteria

• Diagnosis of Parkinson's disease based on MDS-UPDRS criteria (Group 1 and 2)
• Dopaminergic therapy stable with stable dose for at least 4 weeks prior to J0
• Affiliate to a social security or similar system
• Having given written consent to participate in the study, free and informed.
• Having chronic pain more than 3 month (Group 1)
• Without chronic pain (Groupe 2 and 3)
• Having central pain using specific algorithm (Marques et al., 2019)
• Having pain intensity at least 4 on VAS (Visual Analogue Scale) during the last month (Group 1)
• Having pain intensity lower than 3 on VAS (Visual Analogue Scale) during the last month (Group 2 and 3)

Exclusion criteria

• Having atypical Parkinson's disease (Group 1 and 2)
• Parkinson's disease with disabling dyskinesia and/or severe tremor (Group 1 and 2)
• Any contraindications to having a brain MRI or PET scan (e.g., pacemaker, metal foreign body, claustrophobia, deep brain stimulation or apomorphin pump unable to be turn off)
• History of head trauma with loss of consciousness lasting more than 30 minutes
• Not agreeing to be informed in the event of incidental discovery of an abnormality on MRI or during neuropsychological assessment
• Presence of cognitive dysfunction (defined as MoCA score < 24)
• Severe depression (BDI > 29)
• unable to stop the opioid treatment the week before the imaging exam ( e.g., Antarène codéine, Claradol codéine, Codoliprane, Dafalgan codéine, Euphon, Klipal, Lindilane, Néo-codion, Paderyl, Prontalgine, Pulmoserum, Tussipax ; Opium : Izalgi, Lamaline, Colchimax, Dropizal ; Morphine : Actiskenan, Moscontin, Oramorph, Sevredol, Skenan ; Buprénorphine : Bupensan, Buvidal, Orobupre, Sixmo, Suboxone, Subutex, Temgesic, Zubsolv ; Dihydrocodéine : Dicodin ; Hydromorphone : Sophidone ; Nalbuphine : Nalpain ; Fentanyl : Abstral, Actiq, Breakyl, Durogesic, Effentora, Instanyl, Matrifen, Pecfent, Recivit ; Méthadone : Methadone AP-HP, Zorvon ; Oxycodone : Oxsynia, Oxycontin, Oxynorm, Oxynormoro ; Tramadol : Biodalgic, Contramal, Ixprim, Monoalgic, Monocrixo, Orozamudol, Skudexum, Topalgic, Zaldiar, Zamudol, Zumalgic)
• unable to stop any treatment
• Treated with level 1 analgesics (NSAIDs, acetaminophen) or coanalgesics (antidepressants, antiepileptics) unless treatment has been stable for at least 4 weeks prior to the study and does not interfere with the noradrenergic system (list above).
• Presenting or having presented a dependence on any addictive substance according to DSM-IV-TR criteria, with the exception of tobacco.
• Having used recreational drugs interfering with the opioid and noradrenergic systems (cannabis, CBD, opiates, MDMA, ecstasy) in the last 3 months or chronic use
• Pregnant women, women in labor or nursing mothers
• Persons deprived of their liberty by judicial or administrative decision
• Under psychiatric care
• Admitted to a health or social institution for purposes other than research
• Under legal protection (guardianship, curatorship)
• Participant in another interventional study with an exclusion period still in progress at pre-inclusion
• Having exceeded the annual amount of compensation authorized for participation in research protocols

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Basic science

Study locations

France · 3 centers

• Hôpital Neurologique Pierre Wertheimer — Bron
• CHU de Clermont-Ferrand Hôpital Gabriel Montpied — Clermont-Ferrand
• CHU de Toulouse - Hôpital Purpan — Toulouse

Identifiers

NCT: NCT07127146 · 69HCL24_0721

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗