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Liver Cell Transplant for Phenylketonuria

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Disease Information

Descriptive Information
Brief Title † Liver Cell Transplant for Phenylketonuria
Official Title † Hepatocyte Transplantation for Phenylketonuria
Brief Summary The purpose of this research study is to determine whether partial irradiation of the liver and liver cell transplantation can reduce the need for dietary and medical management or could possibly eliminate the need for a special diet and medications to treat this disease for patients with phenylketonuria (PKU) by normalizing phenylalanine levels in the body. Phenylalanine (Phe) is a substance needed in the body that can only be obtained from the foods people eat. People with PKU cannot get rid of Phe in their body. Large amounts of Phe can cause problems, such as deterioration of mental function. At the present time, liver cell transplants are experimental and have been done in only a limited number of human subjects.
Detailed Description Human phenylketonuria (PKU) results from phenylalanine hydroxylase (PAH) deficiency, and represents one of the most common and extensively studied single-gene Mendelian disorders in humans. Unfortunately, optimum clinical outcome demands lifelong dietary restriction through adherence to an unpalatable and expensive artificial diet. Challenges in maintaining traditional therapy lead to increasing phenylalanine (Phe) levels in patients as they approach adulthood with an incumbent severe burden of psychosocial and intellectual difficulties. The recent introduction of the new medication Sapropterin for treatment of PKU has improved Phe control and dietary tolerance in some patients, but at enormous cost to patients and insurers for the FDA designated orphan product. Thus, there is an unmet need for novel therapies to correct PKU. PAH is almost exclusively expressed in the liver in humans. The main objective of the current proposal is to determine the feasibility of hepatocyte transplantation to correct the biochemical (and ultimately, clinical) features of PKU.
Study Phase Phase 1/Phase 2
Study Type † Interventional
Study Design †
Primary Outcome Measure † Improvement/reversal of characteristics of PKU
Secondary Outcome Measure † Engraftment of Hepatocytes
Condition † Phenylketonuria
Intervention † RadiationPreparative Radiation Therapy
Study Arms / Comparison Groups Hepatocyte Transplantation See Below.
Publications *

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information
Recruitment Status † Radiation
Estimated Enrollment † 10
Start Date † December 2011
Completion Date January 2019
Primary Completion Date October 2018
Eligibility Criteria † Inclusion Criteria: Children (14-17 years of age) 1. Previous diagnosis of classical PKU as determined by Phe >20 mg/dl at diagnosis or a PAH mutation known to cause classical PKU 2. Patients have poor control on standard therapy (i.e. Kuvan or diet alone) as defined by two consecutive phe levels of > 12 mg/dl in past 6 months. This is nearly 4 times the recommended level. 3. Baseline I.Q. >70 as assessed by Wechsler Abbreviated Scale of Intelligence (2-subtest IQ) 4. Cognitive or psychological impairment as defined by a score of one standard deviation below the mean in two of the four following assessments: - Wechsler Intelligence Scale for Children-Fourth Addition-Coding Subtest (for individuals up to 16 years, 11 months years of age) OR Wechsler Adult Intelligence Test-Fourth Edition-Coding Subtest (for individuals 17 years of age) - Behavior Rating Inventory of Executive Function (parent version) - Delis-Kaplan Executive Function System (D-KEFS) Verbal Fluency - BASC-II (Behavior Assessment System for Children-Second Addition) 5. Psychological assessment in the past year 6. Must have a complete evaluation including dietary records in PKU clinic. Thereafter, monthly Phe levels will be drawn (per clinical care management for PKU patients) and 3-Day food records will be completed monthly until hepatocyte cells are available. Adults (18 years of age and older) 1. Previous diagnosis of classical PKU as determined by Phe >20 mg/dl at diagnosis or a PAH mutation known to cause classical PKU 2. Patients have poor control on standard therapy (i.e. Kuvan or diet alone) as defined by two consecutive phe levels of > 12 mg/dl in past 6 months. This is double the recommended level. 3. Psychological assessment in the past year 4. I.Q. >70 as assessed by any standardized and validated IQ measure. 5. Must have dietary documentation and a routine clinical evaluation in PKU clinic one month prior to enrollment. Monthly Phe levels will be drawn (per clinical care management for PKU patients) and 3-Day food records will be completed monthly until hepatocyte cells are available. Exclusion Criteria: - I.Q.
Gender All
Ages 14 Years - N/A
Accepts Healthy Volunteers No
Contacts ††
Location Countries † United States
Administrative Information
NCT ID † NCT01465100
Organization ID PRO10100525
Secondary IDs ††
Responsible Party Principal Investigator
Study Sponsor † University of Pittsburgh
Collaborators ††
Investigators † Principal Investigator: Ira J Fox, MD, University of Pittsburgh
Information Provided By
Verification Date June 2017
First Received Date † October 20, 2011
Last Updated Date June 6, 2017
† Required WHO trial registration data element.
†† WHO trial registration data element that is required only if it exists.
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