Treatment of Apomorphine-induced Skin Reactions: a Pilot Study

Study Overview
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Brief Summary
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Skin reactions as a result of continuous subcutaneous apomorphine infusion occur frequently and interfere with the absorption of apomorphine. The histopathology of apomorphine-induced skin reactions is poorly understood. Therefore treatment options are limited and suggestive. Objective: to investigate the efficacy of four treatments including massage, dilution of apomorphine, treatment with topical hydrocortisone and pre-treatment with subcutaneous administered hydrocortisone, in Parkinson's disease patients with apomorphine-induced skin reactions.

Official Title
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Open-label Crossover Trial to Investigate the Efficacy of Treatments in Apomorphine-induced Skin Reactions

Conditions
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Parkinson's Disease, Apomorphine-induced Skin Reactions

Intervention / Treatment
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* Drug: Apomorphine 0.25% (2.5mg/ml)
* Device: Massage with a spiky ball
* Drug: Hydrocortisone cream 1%
* Drug: Subcutaneous hydrocortisone 10mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female and male subjects aged ≥30; Diagnosis of idiopathic Parkinson's disease of >3 years' duration, defined by the United Kingdom (UK) Brain Bank criteria, with the exception of >1 affected relative being allowed, without any other known or suspected cause of Parkinsonism (Gibb & Lees, 1988); Treatment with continuous subcutaneous apomorphine infusion; Having apomorphine-induced skin reactions (i.e. erythema, swelling and/or nodule formation); Male and female patients must be compliant with a highly effective contraceptive method (oral hormonal contraception alone is not considered highly effective and must be used in combination with a barrier method) during the study, if sexually active; Subjects considered reliable and capable of adhering to the protocol, visit schedule, and medication intake according to the judgement of the investigator. Exclusion Criteria: High suspicion of other parkinsonian syndromes; History of respiratory depression; Hypersensitivity to hydrocortisone or any excipients of the medicinal product; Concomitant therapy with histamine antagonist; Known with Cushing's disease or hypercortisolism Any medical condition that is likely to interfere with an adequate participation in the study including e.g. current diagnosis of unstable epilepsy; clinically relevant cardiac dysfunction and/or myocardial infarction or stroke within the last 12 months; Pregnant and breastfeeding women; Current infectious disease with fever at the time of investigation.

Ages Eligible for Study
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Minimum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Massage with a spiky ball<br>Subjects are instructed to massage the apomorphine-induced skin reactions with a spiky ball 3 times a day for 2 minutes for 14 days. | Device: Massage with a spiky ball<br>* Each patient will massage skin reactions with a spiky ball 3 times a day for 2 minutes.<br>|
| Active Comparator: Hydrocortisone cream 1%<br>Subjects are instructed to apply hydrocortisone cream 1% once daily for 14 days. | Drug: Hydrocortisone cream 1%<br>* Hydrocortisone cream 1% (1mg/g) will be administered on each nodule one time a day<br>|
| Active Comparator: Subcutaneous hydrocortisone 10mg<br>Subjects are instructed to administer subcutaneous hydrocortisone (Solu-Cortef 10mg) prior to apomorphine via the subcutaneous infusion line which is used for administration of apomorphine, for 14 days. | Drug: Subcutaneous hydrocortisone 10mg<br>* Subcutaneous hydrocortisone 10mg will be administered previous to apomorphine infusion making use of the apomorphine infusion system<br>* Other names: Solu-Cortef;|
| Active Comparator: Apomorphine 0.25% (2.5mg/ml)<br>Subjects are instructed to dilute apomorphine 0.5% (5mg/ml) with the same volume of physiologic saline (NaCl 0.9%) to 0.25% (2.5mg/ml). Apomorphine will be infused subcutaneously for 14 days. | Drug: Apomorphine 0.25% (2.5mg/ml)<br>* Apomorphine 0.5% (5mg/ml) will be diluted to 0.25% (2.5mg/ml) by the addition of the same volume physiological saline (NaCl 0.9%).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes on global perceived effect scale |  | 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in histological skin tissue characteristics | Histological skin tissue characteristics are presence of eosinophils, melanin-like pigment, fibrosis, lymphocytes and histiocytes. | 14 days | 
| Changes in nodule size (diameter) |  | 14 days | 
| Changes in erythema size (diameter) |  | 14 days | 
| Eosinophilia | Defined as increased absolute eosinophil count | 14 days | 
| Personal or family history of atopic constellation | Assessed with a questionnaire | 14 days | 
| Personal or family history of allergies | Assessed with a questionnaire | 14 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Parkinson's disease, Apomorphine, Infusion, Skin reactions, Subcutaneous nodules, Hydrocortisone, Massage, Dilution