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ISRCTN
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ISRCTN30271509
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ClinicalTrials.gov identifier
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Public title
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The pharmacological basis for the increase in visual time constants induced by single oral doses of sildenafil
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Scientific title
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Acronym
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N/A
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Serial number at source
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N0544183630
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Study hypothesis
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Is the reason that sildenafil (Viagra) causes an increase in the time that the back of the eye perceives a visual image caused by the drug inhibiting phosphodiesterase type 6 (PDE6) in the light receptors in the eye?
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Lay summary
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Ethics approval
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Not provided at time of registration
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Study design
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Randomised controlled trial
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Countries of recruitment
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United Kingdom
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Disease/condition/study domain
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Eye Diseases: Visual sense
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Participants - inclusion criteria
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Healthy male subjects aged 18-55 years. We have decided to only recruit male volunteers because phosphodiesterase inhibitors such as sildenafil and tadalafil are almost exclusively used in male patients.
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Participants - exclusion criteria
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1. Volunteers suffering from any significant medical or psychiatric illness. Subjects may be enrolled at the discretion of the principal investigator or his designated deputy if the illness would not affect the validity of the study or pose an added risk to the subject (e.g. mild asthma, hay fever). Specific conditions that will exclude volunteers from taking part are as follows:
1.1 Cardiac disease
1.2 Blood pressure <90/50mmHg or >160/100mmHg on screening visit
1.3 Renal disease
1.4 Liver disease
1.5 Stroke
1.6 Sickle cell anaemia
1.7 Multiple myeloma
1.8 Leukaemia
1.9 Bleeding disorders
1.10 Peyronie's disease
1.11 Priapism
2. Subjects receiving prescribed medications. Subjects may be included if the medication prescribed would not be considered to affect the validity of the study or pose an added risk to the study subject (e.g. inhaled asthma therapy). Specific exclusions include the following (due to interaction with the study drugs): nitrates, nicorandil, alpha blockers, erythromycin, cimetidine, rifampicin, phenytoin, carbamazepine, Phenobarbital, ritonavir, saquinavir, ketoconazole, itraconazole.
3. Female subjects
4. Subjects with known visual abnormalities other than refractive errors, including specifically: retinitis pigmentosa, optic neuropathy
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Anticipated start date
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24/06/2006
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Anticipated end date
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30/06/2007
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Status of trial
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Completed |
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Patient information material
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Target number of participants
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12 healthy volunteers
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Interventions
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Sildenafil (Viagra) and similar drugs eg tadalafil are phosphodiesterase type 5 inhibitor drugs that have been widely used in the treatment of erectile dysfunction in humans. One of the possible side effects of sildenafil is changes in vision and previous studies have shown that sildenafil can increase visual time constants ie cause a small increase in the length of time that an image is perceived on the back of the eye (retina). This can lead to symptoms of changes in vision for the patient taking the drug.
It has been suggested that the change in vision caused by sildenafil may be due to inhibition of the phosphodiesterase type 6 (PDE6) receptor in the light receptor cells of the eye. Although sildenafil and tadalafil predominantly act to inhibit the PDE5 receptor, sildenafil also has a significant degree of action in inhibiting the PDE6 receptor, whereas tadalafil shows very limited inhibition of this receptor.
We hope to establish whether PDE6 inhibition is the mechanism of the increase in visual time constants caused by sildenafil by performing a series of computerised visual tests to measure visual time constants following dosing with single oral doses of sildenafil, tadalafil or placebo. If PDE6 inhibition is the mechanism of the increase in visual time constants, we should observe changes in the visual time constants with sildenafil, but not tadalafil or placebo.
12 healthy male volunteers aged 18-55 years will be recruited to take part in this study. Volunteers will attend for a screening visit at which written informed consent will be taken and inclusion and exclusion criteria will be checked. A brief medical history will be taken, blood pressure measured and 12-lead electrocardiogram (heart tracing) performed. Vision will be tested to exclude colour blindness and a 20ml sample of venous blood will be taken for DNA analysis to look at differences in the PDE6 gene.
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Primary outcome measure(s)
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Effects of the drugs on retinal time constants (visual persistence and reaction times)
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Secondary outcome measure(s)
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1. Effects of drugs on retinal time constants in different types of photoreceptors
2. Effect of PDE6 genotype on drug effects on retinal time constants
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Sources of funding
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Cambridge Consortium - Addenbrooke's (UK), Own Account NHS R&D Support Funding
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Trial website
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Publications
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No planned publication
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Contact name
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Prof
Morris J
Brown
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Address
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Professor of Clinical Pharmacology
Department of Clinical Pharmacology
Level 6, ACCI, Box 110
Addenbrooke's Hospital
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City/town
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Cambridge
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Zip/Postcode
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CB2 2QQ
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Country
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United Kingdom
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Tel
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+44 01223 762574
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Fax
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+44 01223 762576
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Email
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mjb14@medschl.cam.ac.uk
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Sponsor
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Record Provided by the NHSTCT Register - 2007 Update - Department of Health
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Address
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The Department of Health, Richmond House, 79 Whitehall
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City/town
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London
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Zip/Postcode
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SW1A 2NL
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Country
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United Kingdom
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Tel
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+44 (0)20 7307 2622
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Fax
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+44
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Email
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dhmail@doh.gsi.org.uk
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Sponsor website:
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http://www.dh.gov.uk/Home/fs/en
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Date applied
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28/09/2007
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Last edited
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28/08/2008
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Date ISRCTN assigned
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28/09/2007
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