Parkinson's disease MedDRA version: 18.1 Level: LLT Classification code 10034008 Term: Parkinson's syndrome System Organ Class: 100000004852
Conditions
Sponsors
North Bristol NHS Trust (NBT)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion Criteria 1. Subjects diagnosed with idopathic PD according to the UK Brain Bank Criteria. Bilateral findings must be present at study entry. 2. Duration of PD symptoms 5 years, verified by subject’s medical records. 3. Age 35-75 years. 4. Presence of motor fluctuations. Subjects must have an average of at least 2.5 hours of Off-time per day on 3-day fluctuation diaries completed during screening. 5. Ability to reliably distinguish motor states (ON without dyskinesias, ON with non-troublesome dyskinesias, ON with troublesome dyskinesias and OFF) and accurately complete fluctuation diaries. 6. UPDRS motor score (part III) in a practically defined OFF-state between 25-45. 7. Hoehn and Yahr = stage III in the OFF-state. 8. Responsiveness to levodopa (=40% improvement in motor UPDRS [part III] following a levodopa challenge) 9. No change in anti-parkinsonian medication for 6 weeks before screening. 10. Females of childbearing potential must have a negative pregnancy test at study entry and be willing to use an approved (by the PI or designee) form of contraception until the end of the study. 11. Provision of informed consent. Post-surgery Randomization Criteria 1. No relevant sequelae from catheter implantation such as clinically significant intracerebral trauma, haemorrhage, or infection. 2. Total distribution volume providing at least 50% volume coverage of a predefined volume of interest in each putamen (approximately 25% volume coverage of total putamen), as assessed by an independent review of an MRI scan taken within 2 hours post-infusion of diluent at the end of the healing period. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 30 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 12
Exclusion criteria
Exclusion criteria: 1. Diagnosed with atypical parkinsonism or any known secondary parkinsonian syndrome including but not limited to medication induced, toxic, vascular, post-traumatic or post-infectious parkinsonism, progressive supranuclear palsy, multiple systems atrophy, or other neurodegenerative disorder associated with parkinsonism. 2. Signs or symptoms suggestive of atypical parkinsonian syndrome including supranuclear gaze palsy, early postural instability and falls (within 3 years of disease onset), cerebellar signs, myoclonus, disproportionate antecollis, extensor plantar responses, cortical sensory loss, emotional incontinence (pseudobulbar affect), severe bulbar dysfunction (dysarthria, dysphonia or dysphagia) or respiratory symptoms such as stridor or inspiratory sighs. 3. Family history of more than 1 first-degree relative with PD. 4. Severe dyskinesias or severe tremor which could interfere with GDNF infusion. 5. Prior neurosurgical treatment for PD, including previous treatment with GDNF or deep brain stimulation. 6. Significant neurological disorder other than PD including clinically significant head trauma, cerebrovascular disease, CSF shunt or other implanted CNS device. 7. Presence of significant depression as defined as a Beck Depression Inventory (BDI) score = 20. 8. Current or past history of psychosis requiring therapy. The presence of benign hallucinosis is not exclusionary. 9. Presence or history of clinically significant impulse control disorder or presence or history of dopamine dysregulation syndrome. 10. MoCA score < 24. 11. Use within 3 months of planned catheter insertion of concomitant medications known to affect PD symptoms other than prescribed PD therapy including but not limited to neuroleptics or other central dopamine receptor blockers. 12. Any medical condition which might impair outcome measure assessments or safety measures including ability to undergo MRI scanning. 13. Screening MRI demonstrating any abnormality which would suggest an alternative cause for subject’s parkinsonism. 14. Any medical condition that would put the subject at undue risk from surgical treatment or chronic implants including but not limited to bleeding disorders, chronic infections, or immunosuppressive illness. 15. History within the last 5 years of cancer with the exception of basal cell carcinoma of the skin. 16. History of drug or alcohol abuse within 2 years of planned catheter insertion. 17. Use of any investigational drug or device within 90 days of planned catheter insertion. 18. Active breastfeeding.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the effect of q2 weekly intermittent bilateral intraputamenal GDNF infusions on OFF-state motor function at 9 months.; Secondary Objective: To assess the effect of intermittent bilateral intraputamenal GDNF infusions on ON-state motor function, motor complications, and ON- and OFF-state activities of daily living (ADL) at 9 months. To assess the safety of intermittent bilateral intraputamenal GDNF infusions in a small pilot cohort of subjects and in the full study population. ;Primary end point(s): The primary endpoint of the study is the percentage change from baseline in the practically defined OFF-state Unified Parkinson’s Disease Rating Scale (UPDRS) motor score (part III) after 9 months of double-blind treatment;Timepoint(s) of evaluation of this end point: As specified above | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: For each as specified above ; Secondary end point(s): Efficacy 1. Percentage change from baseline in UPDRS motor score (part III) in the ON-state (following a levodopa challenge) after 9 months of double-blind treatment. 2. Percentage change from baseline in UPDRS ADL score (part II) in the OFF state and in the ON state after 9 months of double-blind treatment. 3. Percentage change from baseline in UPDRS total score (sum of motor + ADL scores) in the OFF state and in the ON state after 9 months of double-blind treatment. 4. Percentage change from baseline in UPDRS mentation, behaviour, and mood score (part I) after 9 months of double-blind treatment. 5. Percentage change from baseline in UPDRS complications of therapy score (part IV) after 9 months of double-blind treatment. 6. Change from baseline in PD diary ratings after 9 months of double-blind treatment; i.e., total OFF-time per day, total good quality ON-time per day(ON without dyskinesias or ON with non-troublesome dyskinesias) and ON-time per day with troublesome dyskinesias. Safety 1. Frequency of device-related adverse events (AEs) during the study period 2. Frequency of treatment-emergent AEs (all treatment-emergent AEs and treatment-emergent AEs related to study drug) during the study period. 3. Frequency of dyskinesias 4. Falls, adverse changes in mood, and impulsivity reported as treatment-emergent AEs during the study period (AEs of special interest). 5. Change from baseline in the Questionnaire for Impulsive-Compulsive Disorders in Parkinson’s Disease (QUIP) every 8 weeks. 6. Change from baseline in the Montreal Cognitive Assessment (MoCA) after 9 months of double-blind treatment. 7. Change f | — |
Countries
United Kingdom
Contacts
Public ContactClinical Trials Manager Helen Lewis
North Bristol NHS Trust (NBT)
Outcome results
None listed