Dopaminergic Modulation of Choroidal Blood Flow Changes During Dark/Light Transitions

Study Overview
=================
Brief Summary
-----------------
There is evidence from a variety of animal studies that choroidal blood flow is under neural control. By contrast, only little information is available from human studies. Recent results indicate that a light/dark transition is associated with a reduction in choroidal blood flow due to an unknown mechanism. We have shown that during unilateral dark/light transitions both eyes react with choroidal vasoconstriction strongly indicating a neural mechanism responsible for the blood flow changes. Dopamine has been discussed as a chemical messenger for light adaptation. However, dopaminergic effects in the eye are not restricted to synaptic sites of release, but dopamine also diffuses to the outer retinal layers and pigment epithelium. Accordingly, dopaminergic effects also include a modulatory role on retinal vessel diameter and animal studies provide evidence for vasodilatory effects in the choroid. There is evidence that during darkness retinal and choroidal dopamine levels decrease. Accordingly, dopamine could provide a modulatory input to the light/dark transition induced changes of choroidal circulation. The aim of the present study is to test this hypothesis.

Official Title
-----------------
Dopaminergic Modulation of Choroidal Blood Flow Changes During Dark/Light Transitions

Conditions
-----------------
Regional Blood Flow, Ocular Physiology

Intervention / Treatment
-----------------
* Drug: Quetiapine (drug)
* Drug: Sulpiride (drug)
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Men aged between 18 and 35 years, nonsmokers Body mass index between 15th and 85th percentile Normal findings in the medical history and physical examination unless the investigator considers an abnormality to be clinically irrelevant Normal laboratory values unless the investigator considers an abnormality to be clinically irrelevant Normal ophthalmic findings, ametropia < 3 Dpt. Exclusion Criteria: Regular use of medication, abuse of alcoholic beverages, participation in a clinical trial in the 3 weeks preceding the study Treatment in the previous 3 weeks with any drug Symptoms of a clinically relevant illness in the 3 weeks before the first study day History of hypersensitivity to the trial drug or to drugs with a similar chemical structure History or presence of gastrointestinal, liver or kidney disease, or other conditions known to interfere with, distribution, metabolism or excretion of study drugs Blood donation during the previous 3 weeks

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>Quetiapine | Drug: Quetiapine (drug)<br>* Quetiapine (Seroquel 100mg-film-coated tablet, AstraZeneca Vienna, Austria) Dose: 100 mg tablet oral single dose<br>Drug: Sulpiride (drug)<br>* Sulpiride (Dogmatil 200mg-tablet, Synthélabo Groupe, Le Plessis Robinson, France) Dose: one half of 200 mg tablet oral single dose<br>Drug: Placebo<br>* Placebo<br>|
| Active Comparator: 2<br>Sulpiride | Drug: Quetiapine (drug)<br>* Quetiapine (Seroquel 100mg-film-coated tablet, AstraZeneca Vienna, Austria) Dose: 100 mg tablet oral single dose<br>Drug: Sulpiride (drug)<br>* Sulpiride (Dogmatil 200mg-tablet, Synthélabo Groupe, Le Plessis Robinson, France) Dose: one half of 200 mg tablet oral single dose<br>Drug: Placebo<br>* Placebo<br>|
| Placebo Comparator: 3<br>Placebo | Drug: Quetiapine (drug)<br>* Quetiapine (Seroquel 100mg-film-coated tablet, AstraZeneca Vienna, Austria) Dose: 100 mg tablet oral single dose<br>Drug: Sulpiride (drug)<br>* Sulpiride (Dogmatil 200mg-tablet, Synthélabo Groupe, Le Plessis Robinson, France) Dose: one half of 200 mg tablet oral single dose<br>Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| choroidal blood flow |  | in total 3x 3 hours | 
| fundus pulsation amplitude |  | in total 3 x 3 hours | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Sulpiride, Quetiapine, Light/dark transition, Choroidal blood flow