Trial record 1 of 1 for:    "Aromatic amino acid decarboxylase deficiency"
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A Clinical Trial for Treatment of Aromatic L-amino Acid Decarboxylase (AADC) Deficiency Using AAV2-hAADC

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified November 2012 by National Taiwan University Hospital
Information provided by (Responsible Party):
National Taiwan University Hospital Identifier:
First received: June 12, 2011
Last updated: December 20, 2012
Last verified: November 2012

The purpose of this study is to determine whether AAV2-hAADC gene therapy is safe and effective in the treatment of aromatic amino acid decarboxylase (AADC) deficiency.

Condition Intervention Phase
Aromatic Amino Acid Decarboxylase Deficiency
Genetic: gene therapy
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Clinical Trial for Treatment of Aromatic L-amino Acid Decarboxylase (AADC) Deficiency Using AAV2-hAADC

Resource links provided by NLM:

Further study details as provided by National Taiwan University Hospital:

Primary Outcome Measures:
  • Serious intracerebral hemorrhage that requires surgical management [ Time Frame: Post-operative day 0 (CT) and day 3 (MRI) ] [ Designated as safety issue: Yes ]
    A CT scan will be done immediately after surgery and an MRI scan will be done around 3 days after the surgery. Any intracerebral hemorrhage will be evaluated to see if a surgical decompression will be necessary

Secondary Outcome Measures:
  • Improvement of PDMS-2 score [ Time Frame: 12th month post surgery ] [ Designated as safety issue: No ]
    PDMS-2 will be performed before and 12 months after the surgery, and the two scores will be compared

  • CSF neurotransmitter levels [ Time Frame: 12th month post surgery ] [ Designated as safety issue: No ]
    A lumbar puncture will be performed both before the surgery and 12 months after surgery. HVA and HIAA levels will be measured and compared.

Estimated Enrollment: 10
Study Start Date: March 2013
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Gene therapy
Intracerebral infusion of AAV2-hAADC viral vector will be performed
Genetic: gene therapy
AAV2-hAADC viral vector will be injected into bilateral putamen by stereotactic surgery.
Other Name: Intracerebral infusion of AAV2-hAADC viral vector

Detailed Description:

Aromatic L-amino acid decarboxylase (AADC) is an enzyme responsible for the final step in the synthesis of neurotransmitters dopamine and serotonin. AADC deficiency is a very rare genetic disorder, but Taiwanese (or Chinese) carry a high prevalence of AADC deficiency due to a founder mutation and patients usually die before the age 5-6 years due to severe motor dysfunction. Gene therapy with adeno-associated virus (AAV) serotype 2 (AAV2) driven human AADC (hAADC) has been tested in Parkinson disease. A compassionate treatment of 4 patients with AADC deficiency by AAV2-hAADC has demonstrated good safety and efficacy. The viral vector will be produced by a GMP facility. Viral vector will be injected directly to bilateral putamens by stereotactic surgery. The safety of the surgery will be monitored by both computed tomography (CT) and magnetic resonance imaging (MRI). Efficacy of the treatment will be monitored by positron emission tomography (PET), cerebral spinal fluid (CSF) neurotransmitter metabolites homovanillic acid (HVA) and 5-Hydroxyindoleacetic acid (5-HIAA) levels, and motor and mental developmental scores.


Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. A definitive diagnosis of AADC deficiency, including a CSF study showing decreased levels of HVA and 5-HIAA, and an elevated dopa level, and the presence of at least one AADC gene pathologic mutation.
  2. The patient must have clinical symptoms of AADC deficiency, include hypotonia, dystonia, and oculogyric crisis.
  3. The patient must be older than 24 months of age or has skull bones suitable for surgery.
  4. The parents of study participants must agree to comply in good faith with the required baseline and follow-up assessments.
  5. The parents or guardians must understand and sign their child's informed consent form.
  6. A compassionate treatment following the available protocol has been done in 4 patients, and 2 more patients are scheduled. The purpose of this compassionate treatment is for life saving before the start of the clinical trial. Patient will be considered on individual basis, and permission from the Review Board is required for each patient.

Exclusion Criteria:

  1. Significant brain malformations
  2. Other significant medical or neurological conditions which would create an unacceptable operative risk. Each case will be individually reviewed and the final decision shall rest with the Primary Investigator.
  3. High preexisting immunity to AAV-2 (≥ 1:1200X or OD>1)
  4. The patient cannot take medicines that will alter the effect of this clinical trial.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01395641

Contact: Wuh-Liang Hwu, MD 886-2-23123456 ext 71938
Contact: Vicky Wu, MS 886-2-23123456 ext 71905

National Taiwan University Hospital Not yet recruiting
Taipei, Taiwan, 100
Contact: Wuh-Liang Hwu, MD    886-2-23123456 ext 71938   
Principal Investigator: Wuh-Liang Hwu, MD         
Sponsors and Collaborators
National Taiwan University Hospital
Principal Investigator: Wuh-Liang Hwu, MD Department of Pediatrics and Medical Genetics, National Taiwan University Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: National Taiwan University Hospital Identifier: NCT01395641     History of Changes
Other Study ID Numbers: 200802042D
Study First Received: June 12, 2011
Last Updated: December 20, 2012
Health Authority: Taiwan: Department of Health

Keywords provided by National Taiwan University Hospital:
aromatic amino acid decarboxylase

Additional relevant MeSH terms:
Amino Acid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases processed this record on August 19, 2014