Clinical Trial: Liver Cell Transplant for Phenylketonuria

Study Status: Suspended
Recruit Status: Suspended
Study Type: Interventional

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 Summary: 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.
Sponsor: University of Pittsburgh

Current Primary Outcome: Improvement/reversal of characteristics of PKU [ Time Frame: 6 months post hepatocyte transplant ]

Measured as a 50% decrease in Phe from baseline study level.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Engraftment of Hepatocytes [ Time Frame: 6 months ]
    Liver biopsy samples may be obtained if a response is ascertained after 6 months. (The approach used, surgical vs percutaneous needle biopsy, will be determined by the clinical setting.)
  • Engraftment of Hepatocytes [ Time Frame: up to one year ]
    Laboratory tests of hepatic function


Original Secondary Outcome: Same as current

Information By: University of Pittsburgh

Dates:
Date Received: October 20, 2011
Date Started: December 2011
Date Completion: May 2017
Last Updated: May 19, 2016
Last Verified: September 2014