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

This study is enrolling participants by invitation only.
Information provided by (Responsible Party):
National Taiwan University Hospital
ClinicalTrials.gov Identifier:
First received: June 12, 2011
Last updated: December 2, 2014
Last verified: December 2014
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
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 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(s) [ Time Frame: 12th month post surgery ] [ Designated as safety issue: No ]
    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: Post-operative day 0, days 3~7, months 3, 6, 9, 12 ] [ Designated as safety issue: Yes ]
    1. Post-surgery intracerebral hemorrhage
    2. Post-surgery CSF leakage
    3. Severity of post-gene therapy dyskinesia (if NG tube feeding is required)

  • Other secondary efficacy end points [ Time Frame: Post-operative months 3, 6, 9, 12 (BW & developmental tests) ; day 0, 12th month (PET) ] [ Designated as safety issue: No ]
    1. Body weight gain
    2. Increase putaminal signal in DOPA-PET study
    3. Increase of score in other developmental tests

  • Exploratory end points [ Time Frame: Baseline, months 3, 6, 9, 12 ] [ Designated as safety issue: No ]
    1. Correlation between anti-AAV2 titer and efficacy
    2. Correlation between age and efficacy

Estimated Enrollment: 10
Study Start Date: August 2014
Estimated Study Completion Date: September 2016
Estimated Primary Completion Date: October 2015 (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 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
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 L-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.

Exclusion criteria

  1. 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.
  2. Preexisting immunity to AAV may limit AAV-mediated gene delivery. Patients with anti-AAV2 antibody titer higher than 1.0 OD will be excluded.
  3. The patient cannot take medicines that will alter the effect of this clinical trial.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov 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
ClinicalTrials.gov Identifier: NCT01395641     History of Changes
Other Study ID Numbers: NTUH-AADC-010 
Study First Received: June 12, 2011
Last Updated: December 2, 2014
Health Authority: Taiwan: Department of Health

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
Anti-Dyskinesia Agents
Antiparkinson Agents

ClinicalTrials.gov processed this record on May 26, 2016