A randomized double blind placebo controlled study to evaluate the modulation of cognitive functions in Parkinson's subjects by sildenafil

• Register: ISRCTN
• Last refreshed on: 17 October 2016
• Main ID: ISRCTN18044132
• Date of registration: 26/09/2005
• Prospective Registration: No
• Primary sponsor: Pfizer Inc. (USA)
• Public title: A randomized double blind placebo controlled study to evaluate the modulation of cognitive functions in Parkinson's subjects by sildenafil
• Scientific title: A randomized double blind placebo controlled study to evaluate the modulation of cognitive functions in Parkinson's subjects by sildenafil
• Date of first enrolment: 14/12/2004
• Target sample size: 100
• Recruitment status: Completed
• URL: http://isrctn.com/ISRCTN18044132
• Study type: Interventional
• Study design: Randomised controlled trial (Treatment)
• Phase: Not Specified

Countries of recruitment

United Kingdom

Contacts

• Name: David Burn

Key inclusion & exclusion criteria

Inclusion criteria: 1. Male or female subjects (excluding women of child bearing potential) between the ages of 50 and 80 years, inclusive
2. Diagnosis of Parkinson's disease according to UK Parkinson's Disease Society Brain Bank Criteria
3. Diagnosis of Parkinson's disease >12 months
4. Mild cognitive impairment insufficient to fulfill Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for dementia, with MMSE score 18-27
5. University of Pennsylvania Smell Identification Test (UPSIT) test score of <30
6. Subjects must be willing and able to provide written informed consent
Exclusion criteria: 1. Subjects with evidence of severe or unstable concomitant medical illness
2. Known hypersensitivity to, or current use of sildenafil, or other PDE5 inhibitors
3. Clinically significant orthostatic hypotension (defined as disabling postural light-headedness or syncopal episodes associated with a fall in systolic blood pressure on standing of over 30 mmHg)
4. Patient taking anti-psychotic or cholinesterase inhibitor medication
5. Patient taking dopamine agonists
6. Major depressive disorder
7. Anosmia secondary to head injury/non-PD related cause
8. Exclusion of patients with Multiple Systems Atrophy
9. Exclusion of patients with colour-blindness
10. Subjects who were prescribed and/or are taking nitrates or nitric oxide donors in any form (oral, sub-lingual, tansdermal, inhalation,aerosols), alpha blockers and/or class IA or III anti-arrhythmic medication
11. Use of medication known or suspected to be potent or moderate inhibitors of cytochrome P4503A4 (excluding ketoconazole, itraconazole, cimetidine, ritonavir)
12. Subjects with congenital QT prolongation
13. Electrocardiogram (ECG) evidence of severe life-threatening rhythm or ischaemic disturbances including acute myocardial infarction (within last year), left bundle branch block, or ventricular tachycardia
14. QTcF prolongation >500 msecs
15. Sustained hypertension >170 mmHg systolic or >110 mmHg diastolic; sustained hypotension <90 mmHg systolic or <50 mmHg diastolic
16. History of regular alcohol abuse within 6 months of screening
17. Treatment with investigational drug within 30 days or 5 half-lives (whichever is longer) preceding the first dose of study medication

Age minimum:
Age maximum:
Gender: Both

Health Condition(s) or Problem(s) studied

Parkinson's disease (PD)
Nervous System Diseases
Parkinson's disease

Intervention(s)

Sildenafil dosing in the treatment group will start at 50 mg once daily for 4 weeks. Dosing is then increased to 100 mg daily for a further 44 weeks. The control group will receive matching placebo teatment for 48 weeks.

Primary Outcome(s)

1. To test if 48 weeks of sildenafil therapy will result in improved cognitive functions in Parkinson's disease subjects as measured by the paired association learning (PAL) test
2. To test if 48 weeks of sildenafil therapy will result in improved olfaction in Parkinson's disease subjects as measured by the UPSIT test

Secondary Outcome(s)

To test if 48 weeks of sildenafil therapy will result in improved motor and cognitive function in Parkinson's disease subjects as measured by the Unified Parkinson's Disease Rating Scale (UPDRS), Dyskinesia Rating Scale, Spatial Working Memory Test and Reaction Time Test.

Secondary ID(s)

A1481189

Source(s) of Monetary Support

Study is fully funded by Pfizer Inc. (USA)