HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Gene therapy for the treatment of hip prosthesis loosening: adverse events in a phase 1 clinical study.

Abstract
Revision surgery for loosened hip prostheses is a heavy burden for elderly patients with comorbidity. As an alternative to surgery we performed a study to stabilize the prosthesis by percutaneous cement injection after removing inflammatory tissue with an intraarticular virus-directed enzyme prodrug approach. Twelve elderly patients with debilitating pain from a loosened hip prosthesis were included in a phase 1 dose-escalating clinical study. The patients were admitted to the hospital for 10 days for an intraarticular vector and prodrug injection, and subsequently for a percutaneous bone cement injection. This paper reports the adverse and serious adverse events of the study. After prodrug injection 9 of 12 patients had gastrointestinal adverse events (nausea, vomiting, and diarrhea), and 8 patients had hepatic adverse events (rise in aspartate aminotransferase and alanine aminotransferase). Five patients developed anemia (World Health Organization grade 1 or 2) from hematomas after cement injection. There were four serious adverse events in the first 6 months after vector injection, but these were not related to gene therapy as judged by an independent safety committee. There was no dose-limiting toxicity. However, the extensive comorbidity in these patients makes it difficult to fully establish the safety of the approach in this small and heterogeneous patient population.
AuthorsJolanda J de Poorter, Rob C Hoeben, Willem R Obermann, Tom W J Huizinga, Rob G H H Nelissen
JournalHuman gene therapy (Hum Gene Ther) Vol. 19 Issue 10 Pg. 1029-38 (Oct 2008) ISSN: 1557-7422 [Electronic] United States
PMID18956951 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antineoplastic Agents
  • Aziridines
  • Escherichia coli Proteins
  • Prodrugs
  • tretazicar
  • NfsB protein, E coli
  • Nitroreductases
Topics
  • Adenoviridae
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents (administration & dosage, adverse effects)
  • Arthroplasty, Replacement, Hip
  • Aziridines (administration & dosage, adverse effects)
  • Escherichia coli Proteins
  • Female
  • Genetic Therapy (adverse effects)
  • Genetic Vectors (administration & dosage, adverse effects)
  • Hip Prosthesis (adverse effects)
  • Humans
  • Male
  • Nitroreductases
  • Pain Management
  • Prodrugs (administration & dosage, adverse effects)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: