GDNF in ideopathicParkinsons Disease

NCT03652363 | Completed Phase 2 DMC

• 1 other identifier: 2553
• Study Type: interventional
• Target: 42
• Locations: 0 countries
• Sites: N/A

Brief Summary

A Placebo Controlled Randomised Trial of GDNF vs placebo The study will require patients to undergo surgery to implant microcatheters precisely into the brain. Patients will then attend clinic on a 2 weekly basis for infusions of a nerve growth factor called GDNF or placebo. Specific tests will also be carried out at regular intervals to assess your symptoms. All participants will undergo radio-isotope brain imaging at the beginning and end of the study. Periodically patients will also be required to undergo an MRI scan to assess the delivery of the study drug or placebo.

Conditions

Idiopathic Parkinson Disease

Outcome Measures

Primary Outcomes (1)

• UPDRS in the off state

  The primary outcome for this study will be the percentage change in motor UPDRS in the practically defined OFF state between baseline and Week 40.

  40 weeks

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Placebo administered via convection enhanced delivery

Drug: glial cell line-derived neurotrophic factor

glial derived neurotrophic factor

EXPERIMENTAL

Recombinant-methionyl human glial cell line-derived neurotrophic factor (r-metHuGDNF), administered via convection enhanced delivery

Drug: glial cell line-derived neurotrophic factor

Interventions

glial cell line-derived neurotrophic factor DRUG

Intermittent Bilateral Intraputamenal Glial Cell Line-Derived Neurotrophic Factor (GDNF) Infusions Administered via Convection Enhanced Delivery

Also known as: GDNF

Placebo; glial derived neurotrophic factor

Eligibility Criteria

• Age: 35 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Subjects diagnosed with idiopathic PD according to the United Kingdom (UK) Brain Bank Criteria. Bilateral findings must be present at study entry.
• Duration of PD ≥ 5 years.
• Age 35-75 years.
• 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.
• 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.
• UPDRS motor score (part III) in a practically defined OFF-state between 25-45.
• Hoehn and Yahr ≤ stage III in the OFF-state.
• Responsiveness to levodopa (\> 40% improvement in motor UPDRS \[part III\] following a levodopa challenge).
• No change in anti-parkinsonian medication for 6 weeks before screening.
• 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.
• Provision of informed consent. -

You may not qualify if:

• Subjects who meet any of the following criteria will NOT be eligible for entry into presurgery and surgery and healing periods of the study:
• 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.
• 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.
• Family history of more than 1 first-degree relative with PD.
• Severe dyskinesias or severe tremor which could interfere with GDNF infusion.
• Prior neurosurgical treatment for PD, including previous treatment with GDNF or deep brain stimulation.
• Significant neurological disorder other than PD including clinically significant head trauma, cerebrovascular disease, CSF shunt or other implanted CNS device.
• Presence of significant depression as defined as a Beck Depression Inventory (BDI) score ≥ 14.
• Presence or history of clinically significant impulse control disorder or presence or history of dopamine dysregulation syndrome.
• MoCA score \< 24.
• 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.
• Any medical condition which might impair outcome measure assessments or safety measures including ability to undergo MRI scanning.
• Screening MRI demonstrating any abnormality which would suggest an alternative cause for subject's parkinsonism.
• 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.
• History within the last 5 years of cancer with the exception of basal cell carcinoma of the skin.

Sponsors & Collaborators

• North Bristol NHS Trust: lead

MeSH Terms

Conditions

Parkinson Disease

Interventions

Glial Cell Line-Derived Neurotrophic Factor

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Glial Cell Line-Derived Neurotrophic Factors; Nerve Growth Factors; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Nerve Tissue Proteins; Biological Factors

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 21, 2018
• First Posted: August 29, 2018
• Study Start: October 25, 2012
• Primary Completion: March 13, 2015
• Study Completion: April 1, 2016
• Last Updated: August 29, 2018

Record last verified: 2018-08