The pharmacological basis for the increase in visual time constants induced by single oral doses of sildenafil

ISRCTN	ISRCTN30271509
DOI	https://doi.org/10.1186/ISRCTN30271509
ClinicalTrials.gov number	NCT00463957
Secondary identifying numbers	N0544183630

Submission date: 28/09/2007
Registration date: 28/09/2007
Last edited: 14/02/2020

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Eye Diseases

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Contact information

Prof Morris J Brown
Scientific

Professor of Clinical Pharmacology
Department of Clinical Pharmacology
Level 6, ACCI, Box 110
Addenbrooke's Hospital
Cambridge
CB2 2QQ
United Kingdom

Phone	+44 01223 762574
Email	mjb14@medschl.cam.ac.uk

Study information

Study design	Randomised controlled trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Scientific title	The pharmacological basis for the increase in visual time constants induced by single oral doses of sildenafil
Study objectives	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(s)	Not provided at time of registration
Health condition(s) or problem(s) studied	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
Pharmaceutical study type(s)
Phase	Not Specified
Drug / device / biological / vaccine name(s)	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 study start date	24/06/2006
Completion date	30/06/2007

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Upper age limit	55 Years
Sex	Male
Target number of participants	12 healthy volunteers
Key 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.
Key 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
Date of first enrolment	24/06/2006
Date of final enrolment	30/06/2007

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

Professor of Clinical Pharmacology

Cambridge
CB2 2QQ
United Kingdom

Sponsor information

Record Provided by the NHSTCT Register - 2007 Update - Department of Health
Government

The Department of Health, Richmond House, 79 Whitehall
London
SW1A 2NL
United Kingdom

Phone	+44 (0)20 7307 2622
Email	dhmail@doh.gsi.org.uk
Website	http://www.dh.gov.uk/Home/fs/en

Funders

Funder type

Government

Cambridge Consortium - Addenbrooke's (UK), Own Account NHS R&D Support Funding

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Editorial Notes

14/02/2020: ClinicalTrials.gov number added. No publications found. All search options exhausted.