AAV2-GDNF for Advanced Parkinson s Disease

NCT01621581 | Completed Phase 1 FDA Drug

• 2 other identifiers: 12013712-N-0137
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

Background: \- Glial cell line-derived neurotrophic factor (GDNF) is a chemical that may help protect and strengthen brain cells that produce dopamine. Dopamine is a chemical that affects brain function. People with Parkinson's disease (PD) have problems producing dopamine in the brain. Researchers want to see if gene transfer can help deliver GDNF into the area of the brain that is damaged by PD. The gene transferred in this study, called AAV2-GDNF, may help produce GDNF to protect the damaged brain cells. Objectives: \- To test the safety and effectiveness of AAV2-GDNF gene transfer for advanced PD. Eligibility: \- Individuals at least 18 years of age who have advanced PD that is not well controlled by medications. Design:

• Participants will be in the study for about 5 years. There will be 18 outpatient study visits and a 3-day stay in the hospital. There may also be overnight stays for followup visits.
• Participants will be screened with a physical exam and medical history. Blood samples will be collected. Tests of PD symptoms and mood and memory will be given. Imaging studies will be used to find the right part of the brain to infuse the gene. The screening visit will take place up to 60 days before surgery.
• Participants will have a baseline visit about a month before the surgery. For 1 week before the baseline visit, participants will keep a diary on any motor problems. The visit will involve movement tests given before and after taking a regular dose of levodopa.
• Participants will have surgery to infuse AAV2-GDNF into the brain. The surgery will also include a lumbar puncture (spinal tap) to collect cerebrospinal fluid. After surgery, participants will recover in the hospital for at least 2 days.
• Participants will have another lumbar puncture 6 and 18 months after surgery. This will be an outpatient visit.
• Participants will have regular followup visits after the surgery. These visits will include neurological tests and movement studies. Visits with a neurosurgeon will take place 1, 2, and 4 weeks after surgery. Additional visits will take place every 3 months for the first 3 years, and then at longer intervals for up to 5 years.

Conditions

Parkinson's Disease

Keywords

Gene Therapy; Parkinson's Disease; Convection-Ehanced Delivery; Viral Vector

Outcome Measures

Primary Outcomes (1)

• Assess the safety and tolerability of 4 different dose levels of AAV2-GDNF

  Treatment-related adverse events

  Day 7, Day 14, 1 Month, 2 Month, 3 Month, 6 Month, 9 Month, 12 Month, 15 Month, 18 Month, 24 Month, 30 Month, 36 Month, 48 Month, 60 Month

Secondary Outcomes (1)

• Obtain preliminary data regarding the potential for clinical responses of the 4 dose levels tested by assessing the magnitude and variability of any treatment effects (via clinical, laboratory and neuroimaging studies).

  12 Years

Study Arms (1)

Single Arm

EXPERIMENTAL

AAV2-GDNF vector will be delivered to each patient

Genetic: Convection enhanced delivery/AAV2-GDNF

Interventions

Convection enhanced delivery/AAV2-GDNF GENETIC

Adeno-Associated Virus Encoding Glial Cell Line-Derived Neurotrophic Factor (AAV2-GDNF) Administered via Bilateral Stereotactic Convection-Enhanced Delivery

Single Arm

Eligibility Criteria

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

You may qualify if:

• Greater than 18 years of age.
• Diagnosed with Idiopathic PD.
• Bradykinesia and
• At least 3 of the following clinical features: resting tremor, cogwheel rigidity, bradykinesia, postural reflex impairment.
• The above clinical features must not be due to trauma, brain tumor, infection, cerebrovascular disease, other known neurological disease (e.g., hereditary form of PD, multiple system atrophy, progressive supranuclear palsy, striatonigral degeneration, Huntington s disease, Wilson s disease), or to known drugs, chemicals or toxicants.
• Disease duration of \> 5 years.
• Hoehn and Yahr Stage III or IV off medication.
• Disability present despite optimal antiparkinsonian medication therapy. Disability will be operationally defined as a Modified Schwab and England Activities of Daily Living Scale score of 80% or lower (during the off state).
• Unified PD Rating Scale (UPDRS) (Fahn et al., 1987) total motor score greater than or equal to 30 in the defined off state.
• Unequivocal responsiveness to levodopa, based on the single-dose levodopa test (as described in the CAPIT and CAPSIT guidelines). A 30% or greater improvement in the UPDRS total motor score will be required to establish unequivocal responsiveness to levodopa.
• Able to provide proper Informed Consent.
• Laboratory values at screening visit (unless other visit specified):
• Platelets \>100,000/mm3 (transfusion independent)
• PT/PTT in normal range and INR less than or equal to 1.3 (on day prior to surgery, if taking anti-coagulants)
• Absolute neutrophil count (ANC) \>1500/mm3

You may not qualify if:

• Presence of prominent oculomotor palsy, cerebellar signs, vocal cord paresis,mean standing blood pressure below 75mmHg, pyramidal tract signs or amyotrophy.
• Genetic PD disorders or with a strong family history of PD.
• Presence of dementia (Montreal Cognitive Assessment less than or equal to 25).
• Received an anti-dementia drug for treatment of cognitive impairment within 30 days of their screening for protocol eligibility.
• Presence or history of psychosis, including if induced by anti-PD medications at doses required to improve motor symptoms.
• Presence of untreated or suboptimally treated depression (Hamilton Depression Scale score \>10) or a history of a serious mood disorder (i.e., requiring psychiatric hospitalization or a prior suicide attempt).
• Presence of substance (drug, alcohol) abuse.
• Contraindication to MRI and/or gadolinium.
• Presence of normal striatal uptake on PET.
• Coagulopathy, anticoagulant therapy, low platelet count, or inability to temporarily stop any antithrombotic medication.
• Prior brain surgery, including GDNF, NTN, GAD, AADC therapy or deep brain stimulation.
• Male or female with reproductive capacity who is unwilling to use barrier contraception throughout the study.
• History of stroke or poorly controlled cardiovascular disease.
• Uncontrolled hypertension or diabetes or any other acute or chronic medical condition that would increase the risks of a neurosurgical procedure.
• History of malignancy (cerebral or systemic) other than treated cutaneous squamous cell or basal cell within the prior 5 years.

Sponsors & Collaborators

• National Institute of Neurological Disorders and Stroke (NINDS): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Airaksinen MS, Saarma M. The GDNF family: signalling, biological functions and therapeutic value. Nat Rev Neurosci. 2002 May;3(5):383-94. doi: 10.1038/nrn812.

  PMID: 11988777 BACKGROUND

• Backman CM, Shan L, Zhang YJ, Hoffer BJ, Leonard S, Troncoso JC, Vonsatel P, Tomac AC. Gene expression patterns for GDNF and its receptors in the human putamen affected by Parkinson's disease: a real-time PCR study. Mol Cell Endocrinol. 2006 Jun 27;252(1-2):160-6. doi: 10.1016/j.mce.2006.03.013. Epub 2006 Apr 27.

  PMID: 16644101 BACKGROUND

• Bjorklund A, Kirik D, Rosenblad C, Georgievska B, Lundberg C, Mandel RJ. Towards a neuroprotective gene therapy for Parkinson's disease: use of adenovirus, AAV and lentivirus vectors for gene transfer of GDNF to the nigrostriatal system in the rat Parkinson model. Brain Res. 2000 Dec 15;886(1-2):82-98. doi: 10.1016/s0006-8993(00)02915-2.

  PMID: 11119690 BACKGROUND

• McFarthing K, Prakash N, Simuni T. CLINICAL TRIAL HIGHLIGHTS: 1. GENE THERAPY FOR PARKINSON'S, 2. PHASE 3 STUDY IN FOCUS - INTEC PHARMA'S ACCORDION PILL, 3. CLINICAL TRIALS RESOURCES. J Parkinsons Dis. 2019;9(2):251-264. doi: 10.3233/JPD-199001. No abstract available.

  PMID: 31127735 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Parkinson Disease

Condition Hierarchy (Ancestors)

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

Study Officials

• John D Heiss, M.D.

  National Institute of Neurological Disorders and Stroke (NINDS)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 14, 2012
• First Posted: June 18, 2012
• Study Start: March 13, 2013
• Primary Completion: February 4, 2022
• Study Completion: February 4, 2022
• Last Updated: April 14, 2026

Record last verified: 2026-03-05

Locations

US (1)