AAV2 GDNF Trial is anyone in this trial or thinking about trying this trial ?

[gettome]

why is this a PD question?

[fronya69 in reply to gettome]

GDNF is a Parkinson's drug that is going to b a nasal spray for P.D. And has great promise! This is y it is a Parkinson question!! thanx Fronya

[Hidden]

This is a clinical trial for Parkinsons !

[batwing7]

Have you any information about it?

[Hidden in reply to batwing7]

Home > Perform a Search > Protocol Details

Protocol Details

A Phase 1 Open-Label Dose Escalation Safety Study of Convection Enhanced Delivery (CED) of Adeno-Associated Virus Encoding Glial Cell Line-Derived Neurotrophic Factor (AAV2-GDNF) in Subjects with Advanced Parkinson's Disease

This study is currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

Number

12-N-0137

Sponsoring Institute

National Institute of Neurological Disorders and Stroke (NINDS)

Recruitment Detail

Type: Participants currently recruited/enrolled

Gender: Male & Female

Min Age: 18

Max Age: N/A

Referral Letter Required

No

Population Exclusion(s)

Children

Special Instructions

Currently Not Provided

Keywords

Gene Therapy;

Parkinson's Disease;

Convection-Ehanced Delivery;

Viral Vector

Recruitment Keyword(s)

None

Condition(s)

Parkinson's Disease

Investigational Drug(s)

AAV2-GDNF

18-Fluorodopa

Investigational Device(s)

None

Intervention(s)

Gene Transfer: Convection enhanced delivery/AAV2-GDNF

Supporting Site

National Institute of Neurological Disorders and Stroke

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.

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Eligibility

INCLUSION CRITERIA:

Greater than 18 years of age.

Diagnosed with Idiopathic PD.

- At least 3 of the following clinical features: resting tremor, cogwheel rigidity, bradykinesia, postural reflex impairment.

- At least one of the above must be resting tremor or bradykinesia.

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 70% 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). In addition to a 33% or greater improvement in one of the timed tasks, 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 baseline visit:

- 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

- Hemoglobin > 10.0 g/dL (transfusion allowed)

- Aspartate aminotransferase or alanine aminotransferase < 2.5 times ULN

- Total bilirubin < 2.5 mg/dL

- Serum creatinine < 1.5 mg/dL

- Serum anti-AAV2 total antibody titer < 1000.

EXCLUSION CRITERIA:

Presence of prominent oculomotor palsy, cerebellar signs, vocal cord paresis, orthostatic hypotension (> 20 mm Hg drop on standing), pyramidal tract signs or amyotrophy.

Genetic PD disorders, including mutations in LRRK, or with a strong family history of PD.

Presence of dementia (Montreal Cognitive Assessment greater than or equal to 25).

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.

Clinically active infection, including acute or chronic scalp infection.

Received investigational agent within 12 weeks prior to screening.

Unable to comply with the procedures of the protocol, including frequent and prolonged follow-up.

Chronic immunosuppressive therapy (e.g., chronic steroids, TNF antagonists, chemotherapy)

Pregnancy or lactation.

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Citations:

The GDNF family: signaling, biological functions and therapeutic value.

Gene expression patterns for GDNF and its receptors in the human putamen affected by Parkinson's disease: a real-time PCR study.

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.

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Contacts:

Principal Investigator

Referral Contact

For more information:

John D. Heiss, M.D.

National Institute of Neurological Disorders and Stroke (NINDS)

Gretchen C. Scott, R.N.

National Institute of Neurological Disorders and Stroke (NINDS)

National Institutes of Health

Building 10

Room 3D20

10 Center Drive

Bethesda, Maryland 20892

Not Listed

[e-mail]

Patient Recruitment and Public Liaison Office

Building 61

10 Cloister Court

Bethesda, Maryland 20892-4754

Toll Free: 1-800-411-1222

TTY: 301-594-9774 (local),1-866-411-1010 (toll free)

Fax: [phone]

[e-mail]

Clinical Trials Number:

NCT01621581

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[Pete-1]

Well that seems to pretty well exclude the whole of the worlds population!

[Jash]

DBS makes me ineligible.

[fronya69 in reply to Jash]

Me too. I want 2 do a clinical trial so badly, but no one wants us if we have DBS. Iv'e been trying 4 yrs.!

[OldJoe]

It seems to leave anyone that has Parkinson's out for sure. I doubt very much if there are any who do not have at least one of the iteems that would make them inadmissable for this trial. I guess it is a trial for nothing and nobody.

[lindah]

I applied for this trial about a month ago, and spoke to Dr. Heiss, who is the new principle investigator. He took my basic information and said one of the study coordinators would call , but i haven't heard from anyone yet. I've been following the progress (really the non-progress ) of this trial for a number of years, and its been postponed many times. The exclusion list is quite long and restrictive - i don't think i'd qualify either.)

I was at the NIH about 2 years ago for another study, related to the GDNF study and spoke to some of the trial coordinators, It seemed they would be screening participants very carefully for phase1, looking for those most likely to respond to the gene therapy. I hope this trial is actually going to begin someday soon. In the meantime if you are interested in participating in this trial, you should go ahead and apply. It might turn out that their "ideal" patient doesn't exist.

[fronya69 in reply to lindah]

lindah, U got that right! U hit it right on the head!! GOD SPEED. fronya

[Hidden]

Is this the same as the trials that are going on at the Franchay Hospital in Bristol, UK?

[petrowoman]

I am in this clinical trial. I had the surgery on March 7, 2014. It is not the same as the trial in Bristol.

The trial in Bristol is using the GDNF protein and a delivery method different from the one in the States.

This trial in the US is using Gene Therapy. A virus has been modified to transport GDNF Genes into the brain of someone with Parkinson's. It is a one time delivery, and the hope is the GDNF genes will reproduce and nourish the ailing neurons. The delivery method has the patient lying in an MRI machine for the entire surgery. The surgeon views the MRI to ensure the gene is going to the correct spot. "ClearPoint" by MRI Interventions provides the delivery hardware & software

[fronya69]

Bring it on. I have such high hopes for this drug 2 help me get my life back. Oh yes, bring it on! When and where! Fronya

[PDadvocate1 in reply to fronya69]

My husband just "disqualified " for this, but it certainly brings great hope! Contact the NIH in Bethesda MD

[sunvox]

Petrowoman,

Can you give us any further information about how you are doing today?