NCT00372320

Effect of AdhAQP1 on Salivary Flow in Patients Treated With Radiation for Head and Neck Cancer

Completed Phase 1 Last updated 11 September 2018

What this trial tests

Phase 1 trial testing Gene Transfer in Parotid Salivary Dysfunction in 17 participants. Completed in 5 September 2018.

Timeline

1 September 2006

Primary endpoint
19 March 2014

5 September 2018

Quick facts

Lead sponsor	National Institute of Dental and Craniofacial Research (NIDCR)
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Primary purpose	treatment
Enrollment	17
Start date	1 September 2006
Primary completion	19 March 2014
Estimated completion	5 September 2018
Sites	1 location across United States

Drugs / interventions tested

• Gene Transfer — full drug profile →
• AdhAQP1 — full drug profile →

Conditions studied

• Parotid Salivary Dysfunction — all drugs for Parotid Salivary Dysfunction →

Sponsor

National Institute of Dental and Craniofacial Research (NIDCR)

Who can join

18 and older, any sex, with Parotid Salivary Dysfunction. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Clinical management of salivary gland hypofunction and xerostomia in head-and-neck cancer patients: successes and barriers.
   Vissink A, Mitchell JB, Baum BJ, Limesand KH, et al · · 2010 · cited 227× · PMID 20970030 · DOI 10.1016/j.ijrobp.2010.06.052
2. Early responses to adenoviral-mediated transfer of the aquaporin-1 cDNA for radiation-induced salivary hypofunction.
   Baum BJ, Alevizos I, Zheng C, Cotrim AP, et al · · 2012 · cited 138× · PMID 23129637 · DOI 10.1073/pnas.1210662109
3. Late responses to adenoviral-mediated transfer of the aquaporin-1 gene for radiation-induced salivary hypofunction.
   Alevizos I, Zheng C, Cotrim AP, Liu S, et al · · 2017 · cited 53× · PMID 27996967 · DOI 10.1038/gt.2016.87
4. Development of a gene transfer-based treatment for radiation-induced salivary hypofunction.
   Baum BJ, Zheng C, Alevizos I, Cotrim AP, et al · · 2010 · cited 46× · PMID 19892587 · DOI 10.1016/j.oraloncology.2009.09.004
5. Insight into Salivary Gland Aquaporins.
   D'Agostino C, Elkashty OA, Chivasso C, Perret J, et al · · 2020 · cited 41× · PMID 32630469 · DOI 10.3390/cells9061547
6. Gene delivery in salivary glands: from the bench to the clinic.
   Samuni Y, Baum BJ. · · 2011 · cited 37× · PMID 21763423 · DOI 10.1016/j.bbadis.2011.06.014
7. Aquaporin-1 gene transfer to correct radiation-induced salivary hypofunction.
   Baum BJ, Zheng C, Cotrim AP, McCullagh L, et al · · 2009 · cited 31× · PMID 19096789 · DOI 10.1007/978-3-540-79885-9_20
8. Transient detection of E1-containing adenovirus in saliva after the delivery of a first-generation adenoviral vector to human parotid gland.
   Zheng C, Nikolov NP, Alevizos I, Cotrim AP, et al · · 2010 · cited 22× · PMID 19941317 · DOI 10.1002/jgm.1416