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Pain in Parkinson's Disease With Motor Fluctuations. (PAINinPD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03648671
Recruitment Status : Recruiting
First Posted : August 27, 2018
Last Update Posted : August 27, 2018
Sponsor:
Collaborator:
Azienda Ospedaliera Universitaria Integrata Verona
Information provided by (Responsible Party):
Michele Tinazzi, MD, PhD, Azienda Ospedaliera Universitaria Integrata Verona

Brief 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).

Condition or disease Intervention/treatment
Parkinson Disease Drug: safinamide metansolfonato (12 weeks) Drug: rasagilina mesilato (12 weeks)

Detailed 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).

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Study Type : Observational
Estimated Enrollment : 48 participants
Observational Model: Cohort
Time Perspective: Prospective
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.
Actual Study Start Date : March 28, 2018
Estimated Primary Completion Date : March 28, 2019
Estimated Study Completion Date : November 30, 2019

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
PD with PAIN
12 patients will undergo add-on drugs therapy with safinamide metansolfonato.
Drug: safinamide metansolfonato (12 weeks)
safinamide metansolfonato

PD without PAIN
12 patients will undergo add-on drugs therapy with safinamide metansolfonato.
Drug: safinamide metansolfonato (12 weeks)
safinamide metansolfonato

PD with PAIN rasagilina
12 patients will undergo add-on drugs therapy with rasagilina mesilato.
Drug: rasagilina mesilato (12 weeks)
rasagilina mesilato

PD without PAIN rasagilina
12 patients will undergo add-on drugs therapy with rasagilina mesilato.
Drug: rasagilina mesilato (12 weeks)
rasagilina mesilato




Primary Outcome Measures :
  1. Latency (ms) of N1/P1 complex. [ Time Frame: Change from baseline at 12 weeks ]
    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.

  2. Latency (ms) of N2/P2 complex. [ Time Frame: Change from baseline at 12 weeks ]
    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.

  3. Amplitude (microvolt) of N1/P1 complex. [ Time Frame: Change from baseline at 12 weeks ]
    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.

  4. Amplitude (microvolt) of N2/P2 complex. [ Time Frame: Change from baseline at 12 weeks ]
    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.


Secondary Outcome Measures :
  1. Body localization [ Time Frame: Change from baseline at 12 weeks ]
    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.

  2. King's Pain Scale for Parkinson's Disease [ Time Frame: Change from baseline at 12 weeks ]
    (score)

  3. Italian version of the brief pain inventory short form [ Time Frame: Change from baseline at 12 weeks ]
    (score)

  4. Clinical global impression of change [ Time Frame: Change from baseline at 12 weeks ]
    (score)

  5. The 39-Item Parkinson's Disease Questionnaire (PDQ-39) [ Time Frame: Change from baseline at 12 weeks ]
    (score)

  6. Numeric Rating Scale (NRS) [ Time Frame: Change from baseline at 12 weeks ]
    (score)

  7. Unified Parkinson's Disease Rating Scale [ Time Frame: Change from baseline at 12 weeks ]
    (score)

  8. Total daily off time [ Time Frame: Change from baseline at 12 weeks ]
    Total daily off time will assessed by patient diaries reporting frequency and duration of the off periods (hours)

  9. Off time following the first morning L-dopa dose [ Time Frame: Change from baseline at 12 weeks ]
    (hours)

  10. Age [ Time Frame: One timepoint ]
    Age

  11. Gender [ Time Frame: One timepoint ]
    (male/female)

  12. Schooling [ Time Frame: One timepoint ]
    (years)

  13. Job [ Time Frame: One timepoint ]
    type of job

  14. Weight [ Time Frame: One timepoint ]
    (kg)

  15. Disease duration [ Time Frame: One timepoint ]
    (years)

  16. Age at PD onset [ Time Frame: One timepoint ]
    (years)

  17. Laterality of PD symptom onset [ Time Frame: One timepoint ]
    (right, left, bilateral)

  18. Most Affected Side [ Time Frame: One timepoint ]
    (right, left, bilateral)

  19. Pain symptoms at PD onset [ Time Frame: One timepoint ]
    (yes, no)

  20. Dominant phenotype [ Time Frame: One timepoint ]
    (Tremor, Bradikinetic/rigid, Mixed)

  21. Modified H&Y [ Time Frame: One timepoint ]
    (score)

  22. Pharmacologic therapy for PD [ Time Frame: One timepoint ]
    Pharmacologic therapy

  23. Comorbilities [ Time Frame: One timepoint ]
    Comorbilities

  24. Mini-Mental State Examination [ Time Frame: One timepoint ]
    (score)

  25. Montreal Cognitive Assessment (MoCA) [ Time Frame: One timepoint ]
    (score)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Males or females patients with mid-to-late PD aged 30 to 80 years with or without chronic pain symptoms (duration >3 months) and motor fluctuations while receiving L-dopa alone or with other dopaminergic treatments.
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03648671


Contacts
Layout table for location contacts
Contact: Michele Tinazzi, MD, PhD 0458027472 ext +39 michele.tinazzi@univr.it
Contact: Christian Geroin, PhD 0458027472 ext +39 christian.geroin@univr.it

Locations
Layout table for location information
Italy
Azienda ospedaliera universitaria integrata verona Recruiting
Verona, Italy, 37126
Contact: Michele Tinazzi, MD, PhD    0458027472    michele.tinazzi@univr.it   
Sponsors and Collaborators
Universita di Verona
Azienda Ospedaliera Universitaria Integrata Verona
Investigators
Layout table for investigator information
Principal Investigator: Michele Tinazzi, MD, PhD Azienda Ospedaliera Universitaria Integrata Verona

Publications:

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Responsible Party: Michele Tinazzi, MD, PhD, Full professor of Neurology, Azienda Ospedaliera Universitaria Integrata Verona
ClinicalTrials.gov Identifier: NCT03648671    
Other Study ID Numbers: 1470CESC
First Posted: August 27, 2018    Key Record Dates
Last Update Posted: August 27, 2018
Last Verified: August 2018

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Michele Tinazzi, MD, PhD, Azienda Ospedaliera Universitaria Integrata Verona:
Safinamide
Pain
Parkinson
Additional relevant MeSH terms:
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Parkinson Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Rasagiline
Monoamine Oxidase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Neuroprotective Agents
Protective Agents
Physiological Effects of Drugs