Safety of a Single Administration of AAV2hAQP1, an Adeno-Associated Viral Vector Encoding Human A… (NCT02446249) | Clinical Trial Compass
Active — Not RecruitingPhase 1
Safety of a Single Administration of AAV2hAQP1, an Adeno-Associated Viral Vector Encoding Human Aquaporin-1 to One Parotid Salivary Gland in People With Irradiation-Induced Parotid Salivary Hypofunction
United States17 participantsStarted 2015-05-04
Plain-language summary
Background:
\- Radiation can cause the parotid salivary glands to make less saliva (dry mouth). This can cause problems like infections and tooth decay. Researchers hope a new drug can help people with dry mouth caused by radiation.
Objectives:
\- To examine the safety of AAV2hAQP1 gene therapy. To see if the drug increases saliva in people whose parotid glands have had radiation.
Eligibility:
\- People at least 18 years of age with a history of radiation therapy for head and neck cancer.
Design:
Participants will be screened in 2 visits with:
* medical history
* physical exam
* scans of the head, neck, and chest
* intravenous administration of glycopyrrolate to stop saliva
* saliva collections
* sialogram which is a procedure in which a substance is injected in the parotid gland and X-rays are taken.
* non-drug infusion
* a small piece of skin being taken
3-5-day hospital stay: Participants will receive the gene infusion. The AAV2hAQP1 will be in a solution in a syringe. It will be slowly pushed into the parotid gland through the parotid duct, an opening in the mouth near the second upper molar tooth.
10 outpatient visits over 3 years. These may include:
* repeats of selected screening tests, including saliva collection
* blood and urine tests
* oral and dental examinations
* head and neck exams, including the use of a thin scope to see the back of the throat
* questionnaires
* a small piece of parotid tissue being taken by either a small scope through the parotid duct or by a small needle guided by ultrasound
* scans of the head and neck. For some, contrast will be injected in a vein
* completion of a diary about how the participant feels between visits
* swabs of teeth and gums to assess the microbiome of the mouth
Who can participate
Age range18 Years
SexALL
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Inclusion criteria
✓. At least 18 years of age
✓. History of external beam radiation therapy for head and neck cancer, with a mean dose equal to or greater than 15 Gy to a parotid gland.
✓. Abnormal parotid gland function as judged by both absence of unstimulated parotid salivary flow and a stimulated parotid salivary flow in the targeted parotid gland \>0 and \<0.3 mL/min/gland after 2% citrate stimulation.
✓. No evidence of recurrence of primary malignancy by otolaryngology (ENT) assessment. Additionally, all patients must have been disease-free of head and neck cancer for at least 5 years, a status to be determined at pre-dose screening using negative clinical exams and PET and or CT imaging of the neck and chest. The anatomic subset of HPV positive oropharyngeal cancer may be enrolled after 2 years post completion of therapy.
✓. Willingness to practice the required birth control method ("barrier" contraception, condoms, diaphragm) until AAV2hAQP1 is no longer detectable in their serum or saliva.
✓. Women who cannot bear children (post-menopausal or due to a surgical intervention) also will be required to practice barrier birth control methods until AAV2hAQP1 is no longer detectable in their serum or saliva.
✓. Ability to stay at the NIH hospital for the period of time necessary to complete each on-site phase of the protocol (3-5 days).
✓. No history of allergies to any medications or agents to be used in this protocol.
Exclusion criteria
✕. Pregnant or lactating women. Women of childbearing potential are required to have a negative serum pregnancy test at screening and a negative urine pregnancy test within 48 hours prior to gene infusion.
✕. Any experimental therapy within 3 months.
✕. Any active respiratory tract infection in the 3 weeks prior to day 1 of the protocol
✕. Active infection that requires the use of intravenous antibiotics and does not resolve at least 1 week before Day 1.
✕. Uncontrolled ischemic heart disease: unstable angina, evidence of active ischemic heart disease on ECG, congestive heart failure (left ventricular ejection fraction \< 45% on MUGA or echo) or cardiomyopathy.
✕. Asthma or chronic obstructive pulmonary disease requiring regular inhaled or systemic corticosteroids.
✕. Individuals with a history of autoimmune diseases affecting salivary glands, including Sjogren's syndrome, lupus, scleroderma, type I diabetes, sarcoidosis, amyloidosis, and chronic graft versus host disease. Organ specific autoimmune conditions may be included if clinically stable.
✕. Use of systemic immunosuppressive medications (,i.e., corticosteroids). Topical corticosteroids are allowed.