Effect of AdhAQP1 on Salivary Flow in Patients Treated With Radiation for Head and Neck Cancer
This study will examine whether the experimental drug AdhAQP1 can increase salivary flow in patients whose parotid glands have been exposed to therapeutic radiation for treatment of head and neck cancer. Radiation may damage the parotid glands (salivary glands located under the skin in front of the ear), leading to dry mouth, infections, excessive tooth decay, mouth sores, difficulty swallowing and pain. AdhAQP1 contains the human aquaporin-1 gene, which codes for a protein that works to transport water across cells, and a virus that normally can cause colds in humans, but is modified to render it ineffective. In animal experiments, AdhAQP1 has increased saliva production for a short time.
Patients between 18 years of age or older who received radiation treatment for head and neck cancer at least 5 years before enrolling in this study, who have no evidence of recurrent tumor, who have dry mouth and who secrete abnormally low levels of saliva from the parotid glands may be eligible for this study. Candidates are screened with a medical history, physical examination, blood, urine and saliva tests, electrocardiogram (EKG), chest x-ray, MRI exam, gallium scan (a nuclear medicine test to look for inflammation in the salivary glands), technetium pertechnetate scan (a nuclear medicine test to examine salivary gland function), parotid sialogram (x-ray of parotid gland), PET and CT scans to look for signs of tumor and a skin biopsy to collect skin cells for use in immunological tests.
Participants have a salt and sugar solution infused through a catheter (plastic tube) into both parotid glands. After 10 minutes, the solution drains into the mouth and is swallowed. Saliva is collected from the parotid glands at 6 and 24 hours after administration of the salt and sugar solution. Ten to 14 days later, patients are admitted to the NIH Clinical Center for up to 4 days for the following tests and procedures:
- On the first day, administration, through a catheter, of the study drug AdhAQP1 into one parotid gland.
- Monitoring over the next 3 days for changes in patients' ability to produce saliva. This includes medical examinations and several blood, urine and saliva collections.
- Technetium scan on day 2.
- Gallium scan on day 2.
Patients return to NIH for follow-up visits at 1, 2, 4, and 6 weeks after the AdhAQP1 infusion and then 3, 4, 5, 6 and 12 months for a medical examination and blood, urine and saliva collections. Gallium, technetium and MRI scans are repeated at several of the follow-up visits, and sialograms are done at 6 and 12 months. Chest x-ray and EKG are repeated at 4 and 6 months.
|Parotid Salivary Dysfunction||Genetic: Gene Transfer Drug: AdhAQP1||Phase 1|
|Study Design:||Primary Purpose: Treatment|
|Official Title:||Open-Label, Dose-Escalation Study Evaluating the Safety of a Single Administration of AdhAQP1, an Adenoviral Vector Encoding Human Aquaporin-1 to One Parotid Salivary Gland in Individuals With Irradiation-Induced Parotid Salivary Hypofunction|
- To evaluate the safety of single doses of escalating doses of AdhAQP1
- To evaluate the effectiveness of AdhAQP1 to increase parotid gland salivary output and improve symptoms associated with irradiation-induced parotid hypofunction.
- To assess salivary flow in the treated parotid gland for up to three years.
|Study Start Date:||August 30, 2006|
|Study Completion Date:||March 19, 2014|
|Primary Completion Date:||March 19, 2014 (Final data collection date for primary outcome measure)|
Please refer to this study by its ClinicalTrials.gov identifier: NCT00372320
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Ilias G Alevizos, D.M.D.||National Institute of Dental and Craniofacial Research (NIDCR)|