GDNF in ideopathicParkinsons Disease

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT03652363
• Date of registration: 21/08/2018
• Prospective Registration: No
• Primary sponsor: North Bristol NHS Trust
• Public title: GDNF in ideopathicParkinsons Disease
• Scientific title: A Placebo-Controlled, Randomised, Double-Blind Trial to Assess the Safety and Efficacy of Intermittent Bilateral Intraputamenal (GDNF) Infusions Administered Via Convection Enhanced Delivery (CED) in Subjects With Parkinson&Apos;s Disease
• Date of first enrolment: October 25, 2012
• Target sample size: 42
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03652363
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 2

Key inclusion & exclusion criteria

Inclusion Criteria:

In order to qualify for entry into the presurgery and surgery and healing periods of the
study, subjects MUST meet all of the following criteria:

1. Subjects diagnosed with idiopathic PD according to the United Kingdom (UK) Brain Bank
Criteria. Bilateral findings must be present at study entry.

2. Duration of PD = 5 years.

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. -

Exclusion Criteria:

Subjects who meet any of the following criteria will NOT be eligible for entry into
presurgery and surgery and healing periods of the study:

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 = 14.

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. 5.3.4 Post-Surgery Randomisation Criteria

In order to be eligible for entry into the double-blind period of the study, subjects must
meet the following criteria after undergoing surgery:

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.



Age minimum: 35 Years
Age maximum: 75 Years
Gender: All

Health Condition(s) or Problem(s) studied

Idiopathic Parkinson Disease

Intervention(s)

Drug: glial cell line-derived neurotrophic factor

Primary Outcome(s)

UPDRS in the off state [Time Frame: 40 weeks]

Secondary ID(s)

2553

Source(s) of Monetary Support

Please refer to primary and secondary sponsors