Pain in Parkinson's Disease With Motor Fluctuations.

Parkinson Disease Clinical Trial

— PAINinPD  

Official title:

Spontaneous and Evoked Pain in Parkinson's Disease With Motor Fluctuations: an Observational, Prospective, Clinical and Neurophysiological Study in Patients Under L-dopa Add on Therapies.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03648671
• Other study ID #: 1470CESC
• Status: Recruiting
• Start date: March 28, 2018
• Est. completion date: November 30, 2019

Study information

• Verified date: August 2018
• Source: Universita di Verona
• Contact: Michele Tinazzi, MD, PhD
• Phone: 0458027472
• Email: michele.tinazzi[@]univr.it
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Pain (spontaneous pain) is a fundamental non-motor symptom (NMS) of Parkinson's disease (PD) that is prevalent throughout the condition and often unrecognized and undertreated. The study of the scalp laser-evoked potentials (LEPs) (evoked pain) allows a non-invasive exploration of pain central pathways in humans. This technique proved useful in elucidating the physiopathology underlying different pain syndromes. This study has been conceived to study spontaneous pain (and/or evoked pain by laser stimulation) in PD patients (with or without pain) with motor fluctuations under drugs-on (Safinamide Metansolfonato or Rasagilina Mesilato).

Description:

Pain (spontaneous pain) is a fundamental non-motor symptom (NMS) of Parkinson's disease (PD) that is prevalent throughout the condition and often unrecognized and undertreated. Different types of pain have been described in association with PD including musculoskeletal, dystonic, central and neuropathic pain. Although musculoskeletal pain is the most commonly reported, a number of patients experience multiple types of pain which are more frequent and disabling in the intermediate phase of disease and which ultimately have a significant negative impact on the patient's quality of life. Despite its relevance, the pathophysiological mechanisms underlying pain in PD are yet to be fully understood. An abnormal nociceptive input processing in the central nervous system leading to hypersensitivity to evoked pain probably underlies all the different pain types experienced by PD patients and also intervene in pain-free PD patients. Additional factors including female gender, depression, disease duration, motor complications, postural abnormalities, medical conditions associated with painful symptoms (osteoporosis, rheumatic or degenerative joint disease,) probably contribute to the quality and distribution of spontaneous pain. Abnormalities in pain processing may be the consequence of decreased basal ganglia dopaminergic neurotransmission, as dopamine has been demonstrated to modulate pain perception in supraspinal regions involved in the pain pathways, including insula, anterior cingulate cortex, thalamus and periaqueductal grey. Furthermore, a neurodegeneration involving non-dopaminergic systems (such as g-aminobutyric acid, glutamate, noradrenaline, and serotonin) that modulate pain processing in other regions of the central nervous systems may also play a relevant role. The variegated pain dimension experienced by PD patients makes its therapeutic management a demanding challenge for clinicians.

The study of the scalp laser-evoked potentials (LEPs) (evoked pain) allows a non-invasive exploration of pain central pathways in humans. This technique proved useful in elucidating the physiopathology underlying different pain syndromes. Some data show that LEPs are altered in PD, in both pain-free PD patients and in PD patients with different kinds of pain, with amplitude reduction in N2/P2 component. Acute levodopa challenge had no effect in normalizing the decreased pain threshold/LEPs observed in PD patients in early Parkinson's disease while in PD patients with motor complications it partially increased pain threshold. This is consistent with the hypothesis that motor complications and pain may share common pathophysiological mechanisms which include not only dopaminergic but also non-dopaminergic systems dysfunction (25).This study has been conceived to study spontaneous pain (and/or evoked pain by laser stimulation) in PD patients (with or without pain) with motor fluctuations under drugs-on (Safinamide Metansolfonato or Rasagilina Mesilato).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 48
• Est. completion date: November 30, 2019
• Est. primary completion date: March 28, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• PD patients with or without pain willing to participate in this study and able to sign the written informed consent

• To be included in the PD with pain group, the patient's intensity of pain must be moderate to severe over the last month, as reported by a numerical rating scores (NRS=4) despite the optimal dopaminergic treatment

• No modification of dopaminergic drugs and analgesic therapy with FANS during the 28 days before starting the enrollment in this study.

• Diagnosis of idiopathic PD of =3 years duration

• Hoehn and Yahr stage I-III during OFF time

• Motor fluctuations (>1.5 hours' OFF time/day)

• Patients who would have been treated with add-on therapy irrespective to the present protocol

Exclusion Criteria:

• Patients under (or with previous assumptions) monoamine oxidase inhibitor therapy.

• Late-stage PD experiencing severe, disabling peak-dose or biphasic dyskinesia, or unpredictable or widely swinging symptom fluctuations

• "de novo" patients, patients in early stage or non-fluctuating patients

• Evidence of dementia (MMSE <24)

• Sign and symptoms suggestive of atypical parkinsonism

• Major psychiatric illnesses

• Severe and progressive medical illnesses

• Concomitant diseases potentially causing acute or chronic pain (i.e., rheumatologic conditions, severe polyneuropathy, and spine injuries)

• Treatments with tri-tetracyclic antidepressants, serotonin-norepinephrine reuptake inhibitors (SNRIs), opioids, neuroleptics, barbiturates and phenothiazines, pregabalin and gabapentin

• Any type of retinopathy

Related Conditions & MeSH terms

• Parkinson Disease

Intervention

Drug:
• safinamide metansolfonato (12 weeks)
safinamide metansolfonato
• safinamide metansolfonato (12 weeks)
safinamide metansolfonato
• rasagilina mesilato (12 weeks)
rasagilina mesilato
• rasagilina mesilato (12 weeks)
rasagilina mesilato

Locations

Country	Name	City	State
Italy	Azienda ospedaliera universitaria integrata verona	Verona

Sponsors (2)

Lead Sponsor	Collaborator
Universita di Verona	Azienda Ospedaliera Universitaria Integrata Verona

Country where clinical trial is conducted

Italy, 

References & Publications (5)

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. — View Citation

Tinazzi M, Del Vesco C, Defazio G, Fincati E, Smania N, Moretto G, Fiaschi A, Le Pera D, Valeriani M. Abnormal processing of the nociceptive input in Parkinson's disease: a study with CO2 laser evoked potentials. Pain. 2008 May;136(1-2):117-24. Epub 2007 Aug 31. — View Citation

Tinazzi M, Recchia S, Simonetto S, Defazio G, Tamburin S, Moretto G, Fiaschi A, Miliucci R, Valeriani M. Hyperalgesia and laser evoked potentials alterations in hemiparkinson: evidence for an abnormal nociceptive processing. J Neurol Sci. 2009 Jan 15;276(1-2):153-8. doi: 10.1016/j.jns.2008.09.023. Epub 2008 Oct 26. — View Citation

Tinazzi M, Recchia S, Simonetto S, Tamburin S, Defazio G, Fiaschi A, Moretto G, Valeriani M. Muscular pain in Parkinson's disease and nociceptive processing assessed with CO2 laser-evoked potentials. Mov Disord. 2010 Jan 30;25(2):213-20. doi: 10.1002/mds.22932. — View Citation

Zambito-Marsala S, Erro R, Bacchin R, Fornasier A, Fabris F, Lo Cascio C, Ferracci F, Morgante F, Tinazzi M. Abnormal nociceptive processing occurs centrally and not peripherally in pain-free Parkinson disease patients: A study with laser-evoked potentials. Parkinsonism Relat Disord. 2017 Jan;34:43-48. doi: 10.1016/j.parkreldis.2016.10.019. Epub 2016 Oct 24. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Latency (ms) of N1/P1 complex.	Laser-evoked potentials (LEPs) to explore the primary pain pathway will be assessed at each visit (V0 and V1). The technique of LEPs recording will be carried out as previously performed by our research group.	Change from baseline at 12 weeks
Primary	Latency (ms) of N2/P2 complex.	Laser-evoked potentials (LEPs) to explore the primary pain pathway will be assessed at each visit (V0 and V1). The technique of LEPs recording will be carried out as previously performed by our research group.	Change from baseline at 12 weeks
Primary	Amplitude (microvolt) of N1/P1 complex.	Laser-evoked potentials (LEPs) to explore the primary pain pathway will be assessed at each visit (V0 and V1). The technique of LEPs recording will be carried out as previously performed by our research group.	Change from baseline at 12 weeks
Primary	Amplitude (microvolt) of N2/P2 complex.	Laser-evoked potentials (LEPs) to explore the primary pain pathway will be assessed at each visit (V0 and V1). The technique of LEPs recording will be carried out as previously performed by our research group.	Change from baseline at 12 weeks
Secondary	Body localization	The presence of pain (yes/no, dichotomous variable) in one or more body parts: head, upper limbs, lower limbs, shoulders, neck, trunk , lumbar back, pelvis, knees.	Change from baseline at 12 weeks
Secondary	King's Pain Scale for Parkinson's Disease	(score)	Change from baseline at 12 weeks
Secondary	Italian version of the brief pain inventory short form	(score)	Change from baseline at 12 weeks
Secondary	Clinical global impression of change	(score)	Change from baseline at 12 weeks
Secondary	The 39-Item Parkinson's Disease Questionnaire (PDQ-39)	(score)	Change from baseline at 12 weeks
Secondary	Numeric Rating Scale (NRS)	(score)	Change from baseline at 12 weeks
Secondary	Unified Parkinson's Disease Rating Scale	(score)	Change from baseline at 12 weeks
Secondary	Total daily off time	Total daily off time will assessed by patient diaries reporting frequency and duration of the off periods (hours)	Change from baseline at 12 weeks
Secondary	Off time following the first morning L-dopa dose	(hours)	Change from baseline at 12 weeks
Secondary	Age	Age	One timepoint
Secondary	Gender	(male/female)	One timepoint
Secondary	Schooling	(years)	One timepoint
Secondary	Job	type of job	One timepoint
Secondary	Weight	(kg)	One timepoint
Secondary	Disease duration	(years)	One timepoint
Secondary	Age at PD onset	(years)	One timepoint
Secondary	Laterality of PD symptom onset	(right, left, bilateral)	One timepoint
Secondary	Most Affected Side	(right, left, bilateral)	One timepoint
Secondary	Pain symptoms at PD onset	(yes, no)	One timepoint
Secondary	Dominant phenotype	(Tremor, Bradikinetic/rigid, Mixed)	One timepoint
Secondary	Modified H&Y	(score)	One timepoint
Secondary	Pharmacologic therapy for PD	Pharmacologic therapy	One timepoint
Secondary	Comorbilities	Comorbilities	One timepoint
Secondary	Mini-Mental State Examination	(score)	One timepoint
Secondary	Montreal Cognitive Assessment (MoCA)	(score)	One timepoint