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Protocol Details

Open-Label, Dose-Escalation Study Evaluating the Safety of a Single Administration of an Adeno-Associated Virus Vector Encoding Human Aquaporin-1 to One Parotid Salivary Gland in Individuals with Irradiation-Induced Parotid Salivary Hypofunction.

This study is NOT currently recruiting participants.

Summary | Eligibility | Citations | Contacts




Sponsoring Institute

National Institute of Dental And Craniofacial Research (NIDCR)

Recruitment Detail

Type: No longer recruiting/follow-up only
Gender: Male & Female
Min Age: 18 Years
Max Age: 100 Years

Referral Letter Required


Population Exclusion(s)

Adults who are or may become unable to consent;
Pregnant Women;


Cancer Survivor;
Head and Neck Cancer;
Cancer of the Tonsil

Recruitment Keyword(s)



Squamous Cell Head and Neck Cancer;
Radiation Induced Xerostomia;
Salivary Hypofunction

Investigational Drug(s)


Investigational Device(s)



Biological/Vaccine: AAV2-hAQP1

Supporting Site

National Institute of Dental and Craniofacial Research


- 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.


- To examine the safety of AAV2hAQP1 gene therapy. To see if the drug increases saliva in people whose parotid glands have had radiation.


- People at least 18 years of age with a history of radiation therapy for head and neck cancer.


- Participants will be screened in 2 visits with:

- medical history

- physical exam

- scans

- saliva collections

- sialogram. A substance is injected in the parotid gland and X-rays are taken.

- non-drug infusion

- IV dose of glycopyrrolate to stop saliva

- 3-day hospital stay: Participants will get the gene infusion. The AAV2hAQP1 will be in a solution in a syringe. It will be slowly pushed through an opening into the gland inside your mouth..

- 10 outpatient visits over 3 years. These may include:

- repeats of screening tests

- blood and urine tests

- oral and head and neck exams, including a thin scope in the airway

- questionnaires

- small piece of skin taken

- small piece of tumor tissue taken by either:

- a small video-scope in the parotid duct that also takes pictures

-or by a small needle guided by ultrasound

- scans. Participants lie in a machine or a scanner The machine may feel close to the body or face. . For some, a substance will be injected in a vein or put in the mouth.<TAB>

- Participants will keep a diary about how they feel before and after the therapy.

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1. At least 18 years of age

2. 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.

3. 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.

4. No evidence of recurrence of primary malignancy by otolaryngology (ENT) assessment. Additionally, all subjects 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. FDG/PET and or CT scans of the neck and chest may be done at the discretion of the ENT clinician. The anatomic subset of HPV positive oropharyngeal cancer may be enrolled after 2 years post completion of therapy.

5. Willingness to practice the required birth control method ("barrier" contraception, condoms, diaphragm) until AAV2hAQP1 is no longer detectable in their serum or saliva.

6. 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.

7. 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).

8. No history of allergies to any medications or agents to be used in this protocol.

9. On stable medications (greater than or equal to 2 months) for any underlying medical conditions at time of vector administration.


1. Pregnant or lactating women. Women of childbearing potential are required to have a negative serum or urine pregnancy test at screening and a negative urine pregnancy test within 48 hours prior to gene infusion.

2. Any experimental therapy within 3 months before Day 1.

3. Any active respiratory tract infection in the 3 weeks prior to Day 1 of the protocol

4. Active infection that requires the use of intravenous antibiotics and does not resolve at least 1 week before Day 1.

5. Uncontrolled ischemic heart disease: unstable angina, evidence of active ischemic heart disease on ECG, congestive heart failure (left ventricular ejection fraction < 45% on multi-gated acquisition [MUGA] scan or echocardiography) or cardiomyopathy.

6. Asthma or chronic obstructive pulmonary disease requiring regular inhaled or systemic corticosteroids.

7. Individuals with a history of systemic autoimmune diseases affecting salivary glands, including Sj(SqrRoot)(Delta)gren 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 (e.g. hypothyroidism, atopic dermatitis).

8. Use of systemic immunosuppressive medications (i.e., corticosteroids). Topical corticosteroids are allowed.

9. Malignancy, other than head and neck, within past 3 years, with the exception of adequately treated basal cell or squamous cell carcinoma of the skin or in situ cervical carcinoma.

10. Active infections including Epstein-Barr virus (EBV), cytomegalovirus (CMV), hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection.

11. White blood cell count <3000/microL or absolute neutrophil count <1500/microL or hemoglobin <10.0 g/dL or platelet count <100,000/microL or absolute lymphocyte count less than or equal to 500/microL.

12. Alanine aminotransferase (ALT) and/or and/or aspartate aminotransferase (AST) > 1.5 times upper limit of normal (ULN) or alkaline phosphatase >1.5 times ULN

13. Serum creatinine > 2 mg/dL.

14. Serum bilirubin measurements (total, direct, indirect) that are outside of the normal range.

15. Individuals who are active cigarette smokers as determined by self-reporting.

16. Individuals who have an allergy to iodine or shellfish and thus are unable to have sialographic evaluations.

17. Individuals who have an allergy or hypersensitivity to glycopyrrolate

18. Individuals whose parotid duct(s) are not clinically accessible on screening sialography.

19. Individuals, who on sialography, have a distal stenosis that would impede vector delivery, and individuals whose parotid volume is > 2.5 mL.

20. Significant concurrent or recently diagnosed (<2 months) medical condition that, in the opinion of the Medically Responsible Investigator, could affect the subject s ability to tolerate or complete the study.

21. Live vaccines within 4 weeks prior to gene infusion.

22. Individuals who have had an adverse response to prednisone (e.g. hallucinations).

23. Individuals with uncontrolled diabetes (glycosylated hemoglobin [HbA1c ] >= 10%).

24. Individuals with untreated severe dental caries, pyorrhea, gingivitis, chronic radiation mucositis or ulceration, erythroplasia, leukoplakia or other pre-malignant conditions.

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Gao R, Yan X, Zheng C, Goldsmith CM, Afione S, Hai B, Xu J, Zhou J, Zhang C, Chiorini JA, Baum BJ, Wang S. AAV2-mediated transfer of the human aquaporin-1 cDNA restores fluid secretion from irradiated miniature pig parotid glands. Gene Ther. 2011 Jan;18(1):38-42. doi: 10.1038/gt.2010.128. Epub 2010 Sep 30.

Baum BJ, Alevizos I, Zheng C, Cotrim AP, Liu S, McCullagh L, Goldsmith CM, Burbelo PD, Citrin DE, Mitchell JB, Nottingham LK, Rudy SF, Van Waes C, Whatley MA, Brahim JS, Chiorini JA, Danielides S, Turner RJ, Patronas NJ, Chen CC, Nikolov NP, Illei GG. Early responses to adenoviral-mediated transfer of the aquaporin-1 cDNA for radiation-induced salivary hypofunction. Proc Natl Acad Sci U S A. 2012 Nov 20;109(47):19403-7. doi: 10.1073/pnas.1210662109. Epub 2012 Nov 5.

Delporte C, O'Connell BC, He X, Lancaster HE, O'Connell AC, Agre P, Baum BJ. Increased fluid secretion after adenoviral-mediated transfer of the aquaporin-1 cDNA to irradiated rat salivary glands. Proc Natl Acad Sci U S A. 1997 Apr 1;94(7):3268-73.

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Principal Investigator

Referral Contact

For more information:

John A. Chiorini, Ph.D.
National Institute of Dental And Craniofacial Research (NIDCR)
National Institutes of Health
Building 10
Room 1N113
10 Center Drive
Bethesda, Maryland 20892
(301) 496-4279

Regina Marie Tabios Reyes
National Institute of Dental And Craniofacial Research (NIDCR)
National Institutes of Health
Building 10
Room 1N113
10 Center Drive
Bethesda, Maryland 20892
(301) 201-8628

Office of Patient Recruitment
National Institutes of Health Clinical Center (CC)
Building 61, 10 Cloister Court
Bethesda, Maryland 20892
Toll Free: 1-800-411-1222
Local Phone: 301-451-4383
TTY: TTY Users Dial 7-1-1

Clinical Trials Number:


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