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

NCT ID: NCT06008704

Last Updated: 2024-05-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

34 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-01-01

Study Completion Date

2026-09-01

Brief Summary

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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).

Detailed Description

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The prevalence of chronic pain in PD can be estimated at 60-80% from several epidemiological studies. Both semiological and pathophysiological classification proposes specific and non-specific pain in PD. While non-specific pain is not directly related to PD but may be aggravated by the disease, specific pain is a direct result of the disease with dystonic pain characterized by painful cramps in relation to motor symptoms and non-systematic central pain such as burning, paresthesia, compression (central parkinsonian pain). A case-control study reported that cramp-like pain and central pain were three times more frequent in parkinsonian patients than in the general population. Pathophysiologically, several studies suggest an abnormal nociceptive integration process in PD patients. Previous studies have indicated that the nociceptive signal is amplified along the pain transmission pathways. This could be related to increased facilitation through central sensitization of pain pathways or decreased inhibition (reduced activity of descending inhibitory control systems). Several recent studies suggest that the noradrenergic and/or serotonergic systems may be involved in the pathophysiology of PD-related pain. Therefore, this project will explore the involvement of the serotonergic system in the pathophysiology of pain using brain neuroimaging in PD patients with central pain.

The present study hypothesize that the binding of the radiotracer \[18F\]-MPPF, allowing in vivo imaging of 5HT1A receptors, will be reduced in PD patients with central pain compared to non-painful PD patients at the level of the median raphe, but also at the level of several brain structures involved in the pain matrix such as the insula, the anterior and posterior cingulate cortex, the orbitofrontal cortex, etc. A correlation between the clinical parameters of pain and the brain structures in which MRP binding is decreased should make it possible to confirm the link between these serotonin binding anomalies and pain. Finally, the morphological and functional MRI study should make it possible to identify structural and functional abnormalities within the pain networks in painful Parkinson's patients.

Conditions

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Parkinson Disease

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

physio-pathological prospective open study
Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Study Groups

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PD patients with central chronic pain

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

Group Type OTHER

Clinical assessment

Intervention Type DIAGNOSTIC_TEST

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

Pain characteristics assessment

Intervention Type 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

MRI

Intervention Type DIAGNOSTIC_TEST

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

Thermotest

Intervention Type DIAGNOSTIC_TEST

The thermotest is performed to assess the pain perception threshold

UPDRS-III Scale

Intervention Type DIAGNOSTIC_TEST

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

[18F]-MPPF PET scan

Intervention Type 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 without pain

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

Group Type OTHER

Clinical assessment

Intervention Type DIAGNOSTIC_TEST

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

Pain characteristics assessment

Intervention Type 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

MRI

Intervention Type DIAGNOSTIC_TEST

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

Thermotest

Intervention Type DIAGNOSTIC_TEST

The thermotest is performed to assess the pain perception threshold

UPDRS-III Scale

Intervention Type DIAGNOSTIC_TEST

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

[18F]-MPPF PET scan

Intervention Type 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

Interventions

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Clinical assessment

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

Intervention Type DIAGNOSTIC_TEST

Pain characteristics assessment

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

Intervention Type DIAGNOSTIC_TEST

MRI

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

Intervention Type DIAGNOSTIC_TEST

Thermotest

The thermotest is performed to assess the pain perception threshold

Intervention Type DIAGNOSTIC_TEST

UPDRS-III Scale

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

Intervention Type DIAGNOSTIC_TEST

[18F]-MPPF PET scan

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

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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Inclusion Criteria

* Patients with PD defined according to United Kingdom Parkinson's Disease Brain Bank (UKPDSBB) criteria
* Patients with stable anti-parkinsonian treatment for at least 4 weeks prior to inclusion
* 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.
* Free, informed and written consent signed by the participant and the investigator (at the latest on the day of inclusion and before any examination required by the research).

• 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.

Exclusion Criteria

* 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
Minimum Eligible Age

40 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University Hospital, Toulouse

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Christine BREFEL-COURBON, MD PhD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Toulouse

Locations

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Centre Hospitalier Universitaire de Toulouse

Toulouse, Haute-Garonne, France

Site Status RECRUITING

Countries

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France

Central Contacts

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Christine BREFEL-COURBON, MD PhD

Role: CONTACT

Facility Contacts

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Christine Brefel-Courbon, MD, PhD

Role: primary

05 61 77 94 91

References

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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.

Reference Type BACKGROUND
PMID: 17101155 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32444557 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 33411732 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 34897100 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19062167 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23462484 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16078219 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19375664 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26096067 (View on PubMed)

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

Reference Type BACKGROUND
PMID: 8038587 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12045674 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20960436 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30706197 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18779422 (View on PubMed)

Other Identifiers

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2022-501123-24

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

RC31/21/0566

Identifier Type: -

Identifier Source: org_study_id

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