Dose Response to Topical Glyceryl Trinitrate in Patients With Raynaud's Phenomenon

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the blood flow response to topical Glyceryl Trinitrate when applied to the skin of patient's fingers with Raynaud's Phenomenon.

Official Title
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A Phase I Trial of the Pharmacodynamic Dose Response to Topical Trinitrate in Patients With Raynaud's Phenomenon

Conditions
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Raynaud's Phenomenon

Intervention / Treatment
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* Drug: placebo cream
* Drug: Glyceryl Trinitrate
* Drug: Glyceryl Trinitrate
* Drug: Glyceryl Trinitrate
* Drug: Glyceryl Trinitrate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female volunteers aged between 18 and 50 inclusive Subject has idiopathic RP (patient may have undifferentiated connective tissue disease with positive ANA) diagnosed for more than two (2) years If a female, subject must be non-pregnant and non-lactating The subject has provided written informed consent prior to admission to this study Exclusion Criteria: History of clinically relevant medical illnesses (not considering RP) that in the Investigator's opinion may jeopardize subject's safety or interfere with participation in the study, including but not limited to hemoglobinopathy, hemophilia, clinically significant retinal abnormalities, unstable hypertension, liver diseases, chronic pulmonary diseases, significant cardiovascular diseases, diabetes, thyroid diseases, gout, psychiatric or psychological disorders, CNS trauma or active seizure disorders, allergic or immunologically mediated disorders History in the past five (5) years of drug or alcohol abuse History in the past five (5) years of vascular migraine or other chronic severe headache History in the past five (5) years of autonomic neuropathy or postural hypotension Unwilling or unable to comply with the restrictions outlined in the protocol Current use of smoking cessation treatment, including nicotine patches History of drug allergies, anaphylaxis or laryngeal oedema, including allergy to GTN, propylene/ethylene glycol or common moisturizing creams Use of any nitrate medication or any phosphodiesterase inhibitor within three (3) days prior to or intended use one (1) day following each dosing with study drug Currently treated for hypertension Currently receiving treatment for prevention and/or treatment of RP Use of any investigational medication within 30 days prior to dosing with study medication or scheduled to receive an investigational drug other than during the course of this study Open skin lesions or pathological condition (including, but not limited to, infection) in the area where the study medication is to be applied Use of topical corticosteroid to the hand or fingers within 10 days of treatment with study drug Withdrawal of consent at any time during the study Any condition, which compromises ability to give informed consent or to communicate with the investigator as required for the completion of this study Previously enrolled in the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 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: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: 1.<br>placebo cream applied to 2 adjacent fingers on non-dominant hand one time | Drug: placebo cream<br>* placebo cream applied to 2 adjacent fingers of non-dominant hand one time<br>|
| Active Comparator: 2<br>0.6mg of Glyceryl Trinitrate topically to 2 adjacent fingers of non-dominant hand | Drug: Glyceryl Trinitrate<br>* 0.6mg of Glyceryl Trinitrate applied to 2 adjacent fingers on non-dominant hand one time<br>|
| Active Comparator: 3<br>1.2mg of Glyceryl Trinitrate topically to 2 adjacent fingers of non-dominant hand one time | Drug: Glyceryl Trinitrate<br>* 1.2mg Glyceryl Trinitrate topically to 2 adjacent fingers of non-dominant hand one time<br>|
| Active Comparator: 4<br>1.8mg Glyceryl Trinitrate topically to 2 adjacent fingers on non-dominant hand one time | Drug: Glyceryl Trinitrate<br>* 1.8mg Glyceryl Trinitrate topically to 2 adjacent fingers of non-dominant hand one time<br>|
| Active Comparator: 5<br>2.4 mg Glyceryl Trinitrate topically to 2 adjacent fingers of non-dominant hand one time | Drug: Glyceryl Trinitrate<br>* 2.4 mg Glyceryl Trinitrate topically to 2 adjacent fingers of non-dominant hand one time<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Investigate vascular responses to topical Glyceryl Trinitrate versus placebo in patients with Raynaud's using laser Doppler imaging to measure blood flow |  | 6 visits no less than 10 hours between visits | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the dose proportionality of the microvascular response to topical Glyceryl Trinitrate |  | 6 visits no less than 10 hours between visits | 
| Compare the systemic versus topical effect of Glyceryl Trinitrate on vascular response. |  | 6 visits no less than 10 hours between visits | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Raynaud's Syndrome, Raynaud's Disease, RP