Pain in Parkinson's Disease: Exploration of the Serotonin System in Positron Emission Tomography (PET [18F]-MPPF)

NCT06008704 | Recruiting

• 2 other identifiers: RC31/21/05662022-501123-24
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

This project will explore the involvement of the serotonin system in the pathophysiology of PD-related central pain. Thus, the serotonin system will be evaluated in PD patients with and without central pain who will benefit from brain positron emission tomography (PET) allowing in vivo imaging of 5HT1A receptors and multimodal brain MRI including morphometric imaging and functional connectivity (resting state acquisition).

Conditions

Parkinson Disease

Keywords

PD-related central pain; PET [18F] MPPF; serotoninergic system; multimodal imaging; pain threshold

Outcome Measures

Primary Outcomes (1)

• Distribution volume ratio of [18F]-MPPF

  The MRP \[18F\]-MPPF marking the 5 HT1A receptors allows the in vivo visualization of serotonergic neurons and it's sensitive to extracellular variations of serotonin

  during the procedure

Secondary Outcomes (8)

• Pain intensity and [18F]-MPPF uptake

  during the procedure

• Functional impairment and [18F]-MPPF uptake

  during the procedure

• Pain perception thresholds and [18F]-MPPF uptake

  during the procedure

• Macrostructural markers

  during the procedure

• Central pain characteristics measured by Visual Analog Score for pain (VAS) and brain macrostructural markers

  during the procedure

Study Arms (2)

PD patients with central chronic pain

OTHER

Patients from both groups will receive the same interventions, the difference between groups is the eligibility criteria. In this arm only patients presenting central chronic pain will be included

Diagnostic Test: Clinical assessment; Diagnostic Test: Pain characteristics assessment; Diagnostic Test: MRI; Diagnostic Test: Thermotest; Diagnostic Test: UPDRS-III Scale; Diagnostic Test: [18F]-MPPF PET scan

PD patients without pain

OTHER

Patients from both groups will receive the same interventions, the difference between groups is the eligibility criteria. In this arm only patients without central chronic pain will be included

Diagnostic Test: Clinical assessment; Diagnostic Test: Pain characteristics assessment; Diagnostic Test: MRI; Diagnostic Test: Thermotest; Diagnostic Test: UPDRS-III Scale; Diagnostic Test: [18F]-MPPF PET scan

Interventions

Clinical assessment DIAGNOSTIC_TEST

The clinical assessment consists on behavioural and motor evaluations to determine the characteristics of the population

PD patients with central chronic pain; PD patients without pain

Pain characteristics assessment DIAGNOSTIC_TEST

The pain characteristics assessment will be made with a variety of scales and questionnaires which allow to identify the extent of central pain and functional impairment

PD patients with central chronic pain; PD patients without pain

MRI DIAGNOSTIC_TEST

The MRI examination allows anatomical imaging, diffusion imaging and functional imaging to measure specific markers

PD patients with central chronic pain; PD patients without pain

Thermotest DIAGNOSTIC_TEST

The thermotest is performed to assess the pain perception threshold

PD patients with central chronic pain; PD patients without pain

UPDRS-III Scale DIAGNOSTIC_TEST

The UPDRS-III scale allows to asses motor functionality of PD patients

PD patients with central chronic pain; PD patients without pain

[18F]-MPPF PET scan DIAGNOSTIC_TEST

The PET scan after injection of \[18F\]-MPPF at a dose of 200 Megabecquerel/kg +/-10% allows in vivo imaging of 5HT1A receptors

PD patients with central chronic pain; PD patients without pain

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with PD defined according to United Kingdom Parkinson's Disease Brain Bank (UKPDSBB) criteria
• Patients with a Montreal Cognitive Assessment (MoCA) score \> 25
• Patients with a Hospital Anxiety and Depression Scale (HADS)-D score ≥ 11
• Person affiliated or benefiting from a social security scheme.
• For patients with pain
• Patients with PD-related central pain defined according to the criteria of Marques et al, 2019
• Patients with chronic central pain (i.e. present for at least 3 months)
• Patients who have average pain over the previous month according to a VAS ≥ 4.
• For patients without pain
• Patients who do not have pain defined as VAS ≤ 4, meaning that it does not interfere with daily activity.

You may not qualify if:

• Patients treated with second line therapy
• Patients with a history of significant psychiatric pathology according to the investigator
• Patients treated with drugs interacting with 5HT1A receptors in the previous 4 weeks
• Patients with contraindication to MRI
• Patients refusing to be informed of an abnormality discovered during brain imaging
• Patients with dyskinesias judged by the investigator to be disabling for imaging.
• Patients under guardianship or other legal protection, deprived of their liberty by judicial or administrative decision
• Pregnant woman, breastfeeding woman

Sponsors & Collaborators

• University Hospital, Toulouse: lead

Study Sites (1)

Centre Hospitalier Universitaire de Toulouse

Toulouse, Haute-Garonne, 31000, France

RECRUITING

Related Publications (14)

• Aznavour N, Zimmer L. [18F]MPPF as a tool for the in vivo imaging of 5-HT1A receptors in animal and human brain. Neuropharmacology. 2007 Mar;52(3):695-707. doi: 10.1016/j.neuropharm.2006.09.023. Epub 2006 Nov 13.

  PMID: 17101155 BACKGROUND

• Boussac M, Arbus C, Dupouy J, Harroch E, Rousseau V, Ory-Magne F, Rascol O, Moreau C, Maltete D, Rouaud T, Meyer M, Houvenaghel JF, Marse C, Tranchant C, Hainque E, Jarraya B, Ansquer S, Bonnet M, Belamri L, Tir M, Marques AR, Danaila T, Eusebio A, Devos D, Brefel-Courbon C; PREDI-STIM study group*. Personality Dimensions Are Associated with Quality of Life in Fluctuating Parkinson's Disease Patients (PSYCHO-STIM). J Parkinsons Dis. 2020;10(3):1057-1066. doi: 10.3233/JPD-191903.

  PMID: 32444557 BACKGROUND

• Boussac M, Arbus C, Dupouy J, Harroch E, Rousseau V, Croiset A, Ory-Magne F, Rascol O, Moreau C, Rolland AS, Maltete D, Rouaud T, Meyer M, Drapier S, Giordana B, Anheim M, Hainque E, Jarraya B, Benatru I, Auzou N, Belamri L, Tir M, Marques AR, Thobois S, Eusebio A, Corvol JC, Devos D, Brefel-Courbon C; PREDI-STIM study group. Personality dimensions of patients can change during the course of parkinson's disease. PLoS One. 2021 Jan 7;16(1):e0245142. doi: 10.1371/journal.pone.0245142. eCollection 2021.

  PMID: 33411732 BACKGROUND

• Boussac M, Arbus C, Klinger H, Eusebio A, Hainque E, Corvol JC, Rascol O, Rousseau V, Harroch E, d'Apollonia CS, Croiset A, Ory-Magne F, De Barros A, Fabbri M, Moreau C, Rolland AS, Benatru I, Anheim M, Marques AR, Maltete D, Drapier S, Jarraya B, Hubsch C, Guehl D, Meyer M, Rouaud T, Giordana B, Tir M, Devos D, Brefel-Courbon C; PREDISTIM study group. Personality Related to Quality-of-Life Improvement After Deep Brain Stimulation in Parkinson's Disease (PSYCHO-STIM II). J Parkinsons Dis. 2022;12(2):699-711. doi: 10.3233/JPD-212883.

  PMID: 34897100 BACKGROUND

• Brefel-Courbon C, Grolleau S, Thalamas C, Bourrel R, Allaria-Lapierre V, Loi R, Micallef-Roll J, Lapeyre-Mestre M. Comparison of chronic analgesic drugs prevalence in Parkinson's disease, other chronic diseases and the general population. Pain. 2009 Jan;141(1-2):14-8. doi: 10.1016/j.pain.2008.04.026. Epub 2008 Dec 4.

  PMID: 19062167 BACKGROUND

• Brefel-Courbon C, Ory-Magne F, Thalamas C, Payoux P, Rascol O. Nociceptive brain activation in patients with neuropathic pain related to Parkinson's disease. Parkinsonism Relat Disord. 2013 May;19(5):548-52. doi: 10.1016/j.parkreldis.2013.02.003. Epub 2013 Feb 23.

  PMID: 23462484 BACKGROUND

• Brefel-Courbon C, Payoux P, Thalamas C, Ory F, Quelven I, Chollet F, Montastruc JL, Rascol O. Effect of levodopa on pain threshold in Parkinson's disease: a clinical and positron emission tomography study. Mov Disord. 2005 Dec;20(12):1557-63. doi: 10.1002/mds.20629.

  PMID: 16078219 BACKGROUND

• Chaudhuri KR, Schapira AH. Non-motor symptoms of Parkinson's disease: dopaminergic pathophysiology and treatment. Lancet Neurol. 2009 May;8(5):464-74. doi: 10.1016/S1474-4422(09)70068-7.

  PMID: 19375664 BACKGROUND

• Chaudhuri KR, Rizos A, Trenkwalder C, Rascol O, Pal S, Martino D, Carroll C, Paviour D, Falup-Pecurariu C, Kessel B, Silverdale M, Todorova A, Sauerbier A, Odin P, Antonini A, Martinez-Martin P; EUROPAR and the IPMDS Non Motor PD Study Group. King's Parkinson's disease pain scale, the first scale for pain in PD: An international validation. Mov Disord. 2015 Oct;30(12):1623-31. doi: 10.1002/mds.26270. Epub 2015 Jun 11.

  PMID: 26096067 BACKGROUND

• Cloninger CR. Temperament and personality. Curr Opin Neurobiol. 1994 Apr;4(2):266-73. doi: 10.1016/0959-4388(94)90083-3.

  PMID: 8038587 BACKGROUND

• Costes N, Merlet I, Zimmer L, Lavenne F, Cinotti L, Delforge J, Luxen A, Pujol JF, Le Bars D. Modeling [18 F]MPPF positron emission tomography kinetics for the determination of 5-hydroxytryptamine(1A) receptor concentration with multiinjection. J Cereb Blood Flow Metab. 2002 Jun;22(6):753-65. doi: 10.1097/00004647-200206000-00014.

  PMID: 12045674 BACKGROUND

• Dellapina E, Gerdelat-Mas A, Ory-Magne F, Pourcel L, Galitzky M, Calvas F, Simonetta-Moreau M, Thalamas C, Payoux P, Brefel-Courbon C. Apomorphine effect on pain threshold in Parkinson's disease: a clinical and positron emission tomography study. Mov Disord. 2011 Jan;26(1):153-7. doi: 10.1002/mds.23406. Epub 2010 Oct 19.

  PMID: 20960436 BACKGROUND

• Dellapina E, Pellaprat J, Adel D, Llido J, Harroch E, Martini JB, Kas A, Salabert AS, Ory-Magne F, Payoux P, Brefel-Courbon C. Dopaminergic denervation using [123I]-FPCIT and pain in Parkinson's disease: a correlation study. J Neural Transm (Vienna). 2019 Mar;126(3):279-287. doi: 10.1007/s00702-019-01974-5. Epub 2019 Jan 31.

  PMID: 30706197 BACKGROUND

• Defazio G, Berardelli A, Fabbrini G, Martino D, Fincati E, Fiaschi A, Moretto G, Abbruzzese G, Marchese R, Bonuccelli U, Del Dotto P, Barone P, De Vivo E, Albanese A, Antonini A, Canesi M, Lopiano L, Zibetti M, Nappi G, Martignoni E, Lamberti P, Tinazzi M. Pain as a nonmotor symptom of Parkinson disease: evidence from a case-control study. Arch Neurol. 2008 Sep;65(9):1191-4. doi: 10.1001/archneurol.2008.2.

  PMID: 18779422 BACKGROUND

MeSH Terms

Conditions

Parkinson Disease

Condition Hierarchy (Ancestors)

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

Study Officials

• Christine BREFEL-COURBON, MD PhD

  University Hospital, Toulouse

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Christine BREFEL-COURBON, MD PhD

CONTACT

33-561777753; Brefel-Courbon Christine <christine.brefel-courbon@univ-tlse3.fr>

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: physio-pathological prospective open study

Study Record Dates

• First Submitted: May 10, 2023
• First Posted: August 24, 2023
• Study Start: January 1, 2024
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: May 11, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)