Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT02437825 |
| Other study ID # |
0102-15-HMO-CTIL |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
Phase 2
|
| First received |
|
| Last updated |
|
| Start date |
October 2015 |
| Est. completion date |
June 2021 |
Study information
| Verified date |
September 2016 |
| Source |
Hadassah Medical Organization |
| Contact |
JEFFREY WEINBERGER, MD |
| Phone |
+972508946423 |
| Email |
jeff[@]hadassah.org.il |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Salivary fistulae have been the bane of surgical salvage in the era of primary chemoradiation
for head and neck (H&N) cancers. The "blame"of prior chemoradiation tissue damage encouraged
compensatory surgical techniques that focused on the insertion of non-irradiated tissue into
the field. This study emphasizes a paradigm shift in the understanding and treatment of
pharyngocutaneous fistulae. The detrimental effects of salivary enzymes on tissue healing and
surgical anastomoses are addressed and novel treatment strategy is outlined.
Description:
After signing an informed consent form, patients scheduled for total laryngectomy or for
composite resections for oral/pharyngeal/laryngeal malignant tumors, will be randomly divided
into two groups of about ten in each. The control group will receive a placebo while the
study group will receive octreotide. All involved in the care of the patients and the
patients themselves will be blinded to the drug given. The rest of the treatment will be
equal in both groups and will adhere to the current departmental protocols in
Otolaryngology/Oral-Maxillofacial Surgery.
The studied drug (Octreotide 100 mcg s/c) or placebo will be administered in the evening
prior to surgery and subsequently for two weeks on a thrice daily basis.
Both groups will remain in hospital postoperatively for a minimum two week period (the
current common practice). In addition to daily wound assessments, including daily grading of
the pharyngocutaneous fistulae (using our grading system), the patients will also be
evaluated for:
Serology:
1. Complete blood count and biochemistry including CRP and amylase will be assessed every 3
days.
2. GlucoChecks will be performed daily.
Imaging:
1. Patients will have an abdominal ultrasound to examine the gallbladder prior to and
following completion of the two-weeks of therapy.
Admission stay:
Fistula prevention or acceleration of healing will be reflected in the admission time;
generally, patients with fistulae suffer prolonged hospital stays.
Quality of Life Evaluation:
Evaluation of patients' quality of life will be based on two assessment scores:
1. Pain evaluation:
Patients will rate their average head and neck region pain intensity with a 0-10 Numeric
Rating Scale (NRS) (comprising 11 integers including 0), where 0 is "no pain" and 10
represent "the worst pain possible". Assessment will include a record of 'current NRS
'-representing current pain and 'NRS maximum' representing maximal recalled pain in the
in the last six months. The NRS highly correlates to other pain assessment scales and is
a valid, reliable and easy to use tool in clinical dental practice.
2. Oral Health Impact Profile (OHIP-14) questionnaire:
The validated Hebrew version of the short OHIP (Oral Health Impact Profile) questionnaire
(OHIP-14) will be used to assess the Oral health-related quality of life (OHRQoL). For each
OHIP-14 question, subjects will be asked how frequently they had experienced the impact in
the last six months. Responses will be made on a 5 point ordinal scale: 0—never , 1—hardly
ever, 2—occasionally, 3— fairly often, and 4—very often. OHRQoL impairment will be
characterized by the OHIP-14 global score, with a potential range of 0 (no adverse impacts
within the last six months) to 56 (all 14 impacts experienced very often within the last six
months). The OHIP-14 includes seven conceptual dimensions of oral health related quality of
life. The dimensions are functional limitation, physical pain, psychological discomfort,
physical disability, psychological disability, social disability and handicap. OHIP-14
domains will be calculated for each of the domains by summing the response scores for the two
corresponding items. Relationships between OHIP-14 score and various socio-demographic
parameters, health-related behaviors and pain scores will be assessed among the study
population.
CBCT sialography:
On order to monitor the progression of the salivary gland healing process a cone beam
computorized tomography (CBCT) sialography will be implemented.
Saliva collection and analysis:
Patients from the 2 groups will be asked not to eat, drink or brush their teeth an hour
before saliva collection. Thereafter, the saliva secretion rate from the affected parotid
gland (in the operative side) will be measured between 8 to 12 AM using the
Carlson-Crittenden collector. Prior to placement of the cup, the buccal mucosa will be dried
with gauze and the Stensen's ducts will be slightly squeezed to locate the ducts' orifices.
Salivary flow will be stimulated with 2% citric acid. Saliva will be collected for a total
time of 5 minutes. Samples will be kept on ice during and after saliva collection.
Thereafter, samples will be centrifuged at 14,000 rpm for 20 min at 4°C. Supernatant will
collected and protein concentration will be determined according to Bradford (Bio-Rad,
Hercules, CA, USA). Several components secreted in saliva will be assessed including:
Cortisolamylase, cytokines, growth factors, elastases and proteinases. Octreotide levels in
saliva will also be assessed. In addition, sialochemical analysis of Na+, K+, Cl-, Ca2+,
PO43-, Mg2+ concentrations will be performed.
Proteomic analysis:
Depending on protein concentrations further analysis may include supplementary
characterization of salivary biomarkers including SDS-PAGE analysis, two-dimensional
analytical gels, mass spectrometry identification and database searching.
Statistics Numerical variables will be presented as means and standard deviations, while
categorized variables will be presented as frequencies and percentages. A Pearson's
correlation coefficient method will be used. Differences between variables will be subjected
to univariate analysis by t-test and ANOVA. The statistical processing will be established by
SPSS 21.0. Statistical level of significance chosen as P < 0.05.
To examine the factors associated OHIP-14 total score in a multivariate model a conceptual
hierarchical multiple regression model will be adopted within the uni-variate data7. This
well-established approach employs sequential adjustments from distal to proximal determinants
of a health condition, with the aim of elucidating their relationships. Conceptual analysis,
contrary to statistical decisions on significant determinants of diseases, adopts a
theoretical ordering. The ordering of variables is conceptually determined in accordance with
the hypothesis which assumes which variables have confounding effects, and which variables
have a modification effect.
