Contact information
Type
Scientific
Primary contact
Prof Morris J Brown
ORCID ID
Contact details
Professor of Clinical Pharmacology
Department of Clinical Pharmacology
Level 6
ACCI
Box 110
Addenbrooke's Hospital
Cambridge
CB2 2QQ
United Kingdom
+44 01223 762574
mjb14@medschl.cam.ac.uk
Additional identifiers
EudraCT number
ClinicalTrials.gov number
NCT00463957
Protocol/serial number
N0544183630
Study information
Scientific title
The pharmacological basis for the increase in visual time constants induced by single oral doses of sildenafil
Acronym
Study hypothesis
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?
Ethics approval
Not provided at time of registration
Study design
Randomised controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Condition
Eye Diseases: Visual sense
Intervention
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.
Intervention type
Drug
Phase
Not Specified
Drug names
sildenafil
Primary outcome measure
Effects of the drugs on retinal time constants (visual persistence and reaction times)
Secondary outcome measures
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
Overall trial start date
24/06/2006
Overall trial end date
30/06/2007
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
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.
Participant type
Patient
Age group
Adult
Gender
Male
Target number of participants
12 healthy volunteers
Participant exclusion criteria
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
Recruitment start date
24/06/2006
Recruitment end date
30/06/2007
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Professor of Clinical Pharmacology
Cambridge
CB2 2QQ
United Kingdom
Sponsor information
Organisation
Record Provided by the NHSTCT Register - 2007 Update - Department of Health
Sponsor details
The Department of Health
Richmond House
79 Whitehall
London
SW1A 2NL
United Kingdom
+44 (0)20 7307 2622
dhmail@doh.gsi.org.uk
Sponsor type
Government
Website
Funders
Funder type
Government
Funder name
Cambridge Consortium - Addenbrooke's (UK), Own Account NHS R&D Support Funding
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list
No planned publication