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A Phase I/II Clinical Trial for Treatment of Aromatic L-amino Acid Decarboxylase (AADC) Deficiency Using AAV2-hAADC (AADC)

This study has been completed.
Information provided by (Responsible Party):
National Taiwan University Hospital Identifier:
First received: June 12, 2011
Last updated: May 16, 2017
Last verified: May 2017
This Phase I/II trial is to prove the efficacy and safety of AAV2-hAADC to treat patients with AADC deficiency.

Condition Intervention Phase
Aromatic L-amino Acid Decarboxylase (AADC) Deficiency Drug: gene therapy Phase 1 Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II 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:
  • Efficacy of the intervention [ Time Frame: 13 months ]
    1. Measurable neurotransmitter metabolite HVA or HIAA levels in CSF one year after gene therapy.
    2. Increase of PDMS-II score more than 10 points one year after gene therapy

Secondary Outcome Measures:
  • Safety of the trial [ Time Frame: 12 months ]
    1. Post-surgery intracerebral hemorrhage
    2. Post-surgery CSF leakage
    3. Severity of post-gene therapy dyskinesia (if NG tube feeding is required)
    4. Incidence of other SAE (we will collect all AEs and their severity information, including treatment-emergent adverse events)

Other Outcome Measures:
  • Other secondary efficacy endpoints [ Time Frame: 13 months ]
    1. Body weight gain
    2. Increase putaminal signal in F-DOPA PET study
    3. Increase of score in other developmental tests

  • Exploratory endpoint [ Time Frame: 13 months ]
    1. Correlation between anti-AAV2 titer and efficacy
    2. Correlation between age and efficacy

Enrollment: 10
Actual Study Start Date: October 1, 2014
Study Completion Date: December 2, 2016
Primary Completion Date: December 2, 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Gene therapy
Intracerebral infusion of AAV2-hAADC viral vector will be performed
Drug: 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 rare genetic disorder. Taiwanese carry a high prevalence of AADC deficiency due to the founder mutation IVS6+4 A>T, 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 both animal models and Phase I clinical trials of Parkinson disease. We have done a compassionate treatment of 8 patients with AADC deficiency by AAV2-hAADC and demonstrated a result that among the treated patients, 4 could stand with support, 3 could sit with support, and there was no virus-associated toxicity. The longest follow up has exceeded 4 years.

This study is to prove the safety and efficacy of AAV2-hAADC treatment for patients with Aromatic L-amino acid decarboxylase (AADC) deficiency.


Ages Eligible for Study:   24 Months and older   (Child, Adult, Senior)
Sexes Eligible for Study:   All
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 L-dopa level, and the presence of at least one AADC gene pathologic mutation.
  2. Typical clinical manifestations of the disease, such as oculogyric crisis, hypotonia and delayed development.
  3. Over 2 years of age, or has skull bones suitable for surgery.
  4. Participating patient must be fully cooperative for assessments and tests conducted before and throughout the entire trial.
  5. The parents or guardians must sign the Informed Consent Form to give their consent.

Exclusion criteria

  1. Obvious brain structural change in the judgment of the investigator.
  2. The subject will be excluded if there is any health or neurological concern which might increase the risk of surgery. The principal investigator has the right to assess whether the subject is eligible for this trial based on the subject's health condition.
  3. Patients with anti-AAV2 antibody titer higher than 1,200, or >1 O.D. value by ELISA will be excluded.
  4. Subject participating in this trial must not take any drug that might compromise 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

National Taiwan University Hospital
Taipei, Taiwan, 100
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:
Responsible Party: National Taiwan University Hospital Identifier: NCT01395641     History of Changes
Other Study ID Numbers: NTUH-AADC-010
Study First Received: June 12, 2011
Last Updated: May 16, 2017

Keywords provided by National Taiwan University Hospital:
Aromatic Amino Acid Decarboxylase
Gene Therapy
Viral Vector
Gene Transfer
Aromatic L-Amino Acid Decarboxylase Deficiency

Additional relevant MeSH terms:
Dopa Decarboxylase
Antiparkinson Agents
Anti-Dyskinesia Agents processed this record on September 21, 2017