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
|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 2006|
|Study Completion Date:||March 2014|
|Primary Completion Date:||March 2014 (Final data collection date for primary outcome measure)|
Genetic: Gene Transfer
The treatment of most head and neck cancer patients includes ionizing radiation (IR). Salivary glands in the IR field suffer irreversible damage. There is no conventional treatment available to correct this condition. Our research group has been developing the AdhAQP1 recombinant serotype 5 adenoviral (rAd5) vector based on the hypothesis that a replication deficient rAd5 vector is capable of safely transferring the human aquaporin-1 (hAQP1) cDNA to parotid glands of adult patients with IR-induced salivary hypofunction, resulting in an elevated salivary output, albeit transiently. Salivary glands have proven to be valuable gene transfer targets in numerous pre-clinical animal model studies. hAQP1, the archetypal water channel, is a plasma membrane protein that facilitates water movement across lipid bilayers. Rat and minipig studies have clearly shown that the AdhAQP1 strategy for restoring salivary flow to IR-damaged salivary glands is effective, and studies in rats, non-human primates and minipigs have shown that AdhAQP1 and similar rAd5 vectors are without significant untoward effects after salivary gland delivery. The purpose of this clinical protocol is to test the safety of AdhAQP1, with some measures of efficacy, in adult patients with established IR-induced parotid gland hypofunction. The targeted tissue site for the AdhAQP1 vector in the proposed study is a single parotid gland. In this Phase 1 dose-escalation study, safety will be evaluated using conventional clinical and immunological parameters. The primary outcome measure for biological efficacy will be parotid gland salivary output.
|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)|