Apomorphine Effects on Pain in Parkinson's Disease

Apomorphine Effect on Pain in Parkinson's Disease: A Randomized, Double-blind Placebo Cross-over Study

To study the effects of acute apomorphine vs. placebo administration on different Parkinson's disease pain types.

Study Overview

• Status: Recruiting
• Conditions: Parkinson Disease
• Intervention / Treatment: Drug: Apomorphine Injectable Solution; Drug: Placebo

Detailed Description

Apomorphine is the only anti-parkinsonian agent compatible with levodopa in improving Parkinson's disease (PD) motor symptoms. Besides, it has positive effects on some of the nonmotor symptoms of the disease, such as urinary disturbances and sleep. Apomorphine is usually well tolerated as it produces limited side effects. Knowledge about the effects of apomorphine on pain in PD is scarce. Evidence on this topic has only been reported in case reports or small studies but represents a potentially important use of the drug. We hypothesize that apomorphine may be a rational, safe, and useful treatment for subjects with pain in PD, including different subtypes. Within this framework, the present study will evaluate the effect of acute apomorphine vs. placebo administration on different PD pain types.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Veronica Bruno, MD, MPH; Phone Number: 403-220-7572; Email: veronica.bruno@ucalgary.ca
• Study Contact Backup: Name: Beatrice Anghelescu; Phone Number: 403-220-7572; Email: bamanghe@ucalgary.ca

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N4N1
      • Recruiting
      • Movement Disorder Program, Foothills Medical Center, Alberta Health Services
      • Contact: Veronica Bruno, MD, MPH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects with PD according to the MDS Clinical diagnostic criteria for Parkinson's disease.
• Participants on antiparkinsonian medication in advanced stages of the disease and experiencing OFF periods and pain.
• Apomorphine treatment naïve subjects or not received any within the last six months.
• Stable PD and pain medications for at least 30 days.
• Competence to self-report pain severity in the King's Parkinson's disease Pain Scale and a Likert Visual Analogue Scale.

Exclusion Criteria:

• Subjects who are unable to self-report pain severity in the selected scales. Patients that may require a translator or are illiterate will be included if they can self-report pain severity.
• Subjects with a diagnosis of dementia (Montreal Cognitive Assessment <20).
• Subject with poorly controlled orthostatic hypotension.
• Subjects associated with another medical condition, e.g., any cardiovascular, renal or hepatic impairment, hematological or psychiatric diseases.

Any contraindication to receiving apomorphine injections:

• Subjects who are hypersensitive to apomorphine or any ingredient in the formulation or component of the container (hydrochloric acid concentrated, sodium bisulfite (E222), and water)
• Subjects using concomitant drugs of the 5HT3 antagonist class including (e.g., ondansetron, granisetron, palonosetron)
• Subjects using concomitant antihypertensive medications or vasodilators
• Subjects with prolonged QT on an electrocardiogram.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Apomorphine Injections	Drug: Apomorphine Injectable Solution; Patients will receive the treatment while they are in an OFF period, without the effect of any antiparkinsonian medication. For this study, the initial dose of apomorphine or placebo will be 2 mg. We selected an initial standardized dose based on the pharmacological characteristics of apomorphine. Assessments will be completed 30 and 60 minutes after the initial dose. At 60 minutes from the first dose, a 3 mg dose will be administered, and again, assessments will be completed after 30 and 60 minutes. The total given dosage will be 5 mg. Blood pressure and pulse will be checked every 20 minutes after injections. Other Names: Movapo
Placebo Comparator: Placebo Injections	Drug: Placebo; 0.9% saline placebo injection Other Names: • Saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Unified Parkinson Disease Rating Scale	Measures changes of symptom severity, treatment response and the efficacy of treatments. Part 1 (non-motor experiences of daily living), Part 2 (motor experiences of daily living), Part 3 (motor examination) and Part 4 (motor complications). The maximum score for all the parts is 272. Higher scores are indicative of worse outcomes.	0, 1 and 2 weeks
Change in Likert Visual Analogue Scale	The measure of global pain change perceived by the patients. The most simple Likert Visual Analogue Scale is a straight horizontal line of fixed length, usually 100 mm. The ends are defined as the extreme limits of the parameter to be measured (symptom, pain, health) orientated from the left (worst) to the right (best). There are no numerical values on this scale however, a positioning towards the left of the scale indicates a worse outcome.	0, 1 and 2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Clinical Global Impression Scale	Changes in scores on the Clinical Global Impression (CGI) scale. CGI is rated on a 7-point scale, with the severity of illness scale using a range of responses from 1 (normal) through to 7 (amongst the most severely ill patients).CGI scores range from 1 (very much improved) through to 7 (very much worse). Treatment response ratings should take account of both therapeutic efficacy and treatment-related adverse events and range from 0 (marked improvement and no side-effects) and 4 (unchanged or worse and side-effects outweigh the therapeutic effects). Each component of the CGI is rated separately; the instrument does not yield a global score.	0, 1 and 2 weeks
Number of adverse events	Adverse events assessed for safety purposes at each study visit.	0, 1 and 2 weeks

Collaborators and Investigators

• Sponsor: University of Calgary
• Collaborators: Paladin Labs Inc.
• Investigators: Principal Investigator: Veronica Bruno, MD, MPH, University of Calgary

Study record dates

Study Major Dates

• Study Start (Actual): February 28, 2022
• Primary Completion (Anticipated): February 1, 2023
• Study Completion (Anticipated): July 1, 2023

Study Registration Dates

• First Submitted: May 4, 2021
• First Submitted That Met QC Criteria: May 4, 2021
• First Posted (Actual): May 10, 2021

Study Record Updates

• Last Update Posted (Actual): May 18, 2022
• Last Update Submitted That Met QC Criteria: May 16, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Gastrointestinal Agents; Dopamine Agonists; Dopamine Agents; Emetics; Apomorphine
• Other Study ID Numbers: REB20-0423

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No