Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622001439730
Ethics application status
Approved
Date submitted
1/04/2022
Date registered
10/11/2022
Date last updated
10/11/2022
Date data sharing statement initially provided
10/11/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Assessing lymphatic drainage of the normal splenic flexure by single-photon emission computerised tomography (SPECT) technology – A feasibility study
Scientific title
Assessing lymphatic drainage of the splenic flexure by single-photon emission computerised tomography (SPECT) in healthy adults undergoing routine colonoscopy – A feasibility study
Secondary ID [1] 306690 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Lymphatic drainage of the splenic flexure 325640 0
Condition category
Condition code
Cancer 322997 322997 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a research study looking to better understand how a specific portion of the colon functions. The aim of the study is to see how the colon situated in the left upper quarter of the abdomen, near the spleen (i.e., splenic flexure), manages to drain its tissue fluid (i.e., lymph). So far, lymphatic drainage of this part of the colon remains incompletely understood.

The study is being conducted within the Department of Colorectal Surgery at Concord Hospital, Sydney Local Health District (SLHD) by Dr Krishanth Naidu, under the supervision of A/Prof Matthew Rickard, A/Prof Robert Russo and Dr Kheng-Seong Ng.

A Participant Information Sheet (PIS) will inform participants about what is involved in the study and help them decide whether they wish to take part.

2. Study Procedures
The study procedure will take place within the Concord Repatriation General Hospital. Participants will be included into the study only if they have a normal colonoscopy.

During the test
Part 1
Once a normal colonoscopy is performed (standard of care), the area of interest (i.e., splenic flexure) is explored (research component). A special tracer (described below) is placed using the scope to trace the lymphatics.

Part 2
Single photon-emission computed tomography (SPECT) is a test that uses a special type of camera and a tracer (a radioactive substance in liquid form) to look at organs in the body. With this study, the tracer is injected into a small portion of the participant's colon that we are interested in (close to the spleen) to trace the lymph flow of the region. After that, in the Nuclear Medicine Department, a special camera records where the tracer has moved to. As part of the SPECT, participants are required to lie still in a scanner for at least 30 minutes.
After the SPECT scan, participants will complete their recovery, if indicated, and subsequently discharged home. Participants are advised not to drive or operate heavy machinery after their colonoscopy. A follow-up phone call will be made at 1,7 and 30 days from SPECT to understand how participants are going. This will be in the form of a very brief telephone questionnaire.

After the test
Most of the radioactive tracer leaves the body through the urine within a few hours after the SPECT scan. We advise participants to drink more fluids, after the SPECT scan to help flush the tracer from the body. The body breaks down the remaining tracer over the next few days.

Before the test
No extra preparation is required before the SPECT.

It is important that women participating in this study are not pregnant, breast-feeding or directly caring for young children (<5years old). Woman of child-bearing potential, may be required to perform a pregnancy (urine) test before enrolment in the study.

Time commitment
The total time commitment for this study is approximately 4 hours, not including the follow-up phone calls.

Participants agreeing to participate in this study, you will be directed to an online platform for completion of an electronic consent (e-consent) prior to participating. Future use of non-identifiable information may be used for research purposes. In this instance approval from the relevant Human Research Ethics Committee is required to access it and any identifiable data.

Description of intervention
1. Details of the colonoscopy:
A. As a standard of care, a complete colonoscopy (to investigate presenting symptoms/signs) is performed prior to dedicated interrogation of the splenic flexure (SF) with submucosal radio tracer. If lesions are noted that require biopsy, tattooing, clipping or other intervention, the participant is excluded from the study.
B. The standard of care colonoscopy will be performed by the treating clinician.
C. The apex of the SF is defined as the highest and most angulated point of the colon between the transverse colon and the descending colon, assessed visually by the investigator. This is further supported with a visual aid by way of a scope guide that defines the real time position of the scope. A Bluetooth® link is established between the scope guide transducer in the endoscope and the receiving screen. Furthermore, the architecture of the transverse colon compared to the descending and ascending colon, adds to localisation of the SF.

2. Radio tracer placement
A. Technetium-99 (Tc-99m) is reconstituted in the Nuclear Medicine Department with a nano colloid – Nanoscan (Media Radiopharma, Hungary). A Nanoscan vial contains 500mcg of nano colloidal human albumin. This is reconstituted with sodium pertechnetate (Tc-99m) solution for submucosal injection. 40MBq of Tc-99m reconstituted to 0.5ml will be injected. At colonoscopy Tc-99m nano-colloid will be injected through the standard colonoscopic working port.
B. A 23gauge (0.6mm diameter) 5mm Carr-Locke injection needle (Steris Endoscopy, Device Technologies, USA) is used for instillation of the radio isotope. This needle has automatic retraction technology to limit inadvertent needle stick and spillage. This needle is housed within a 2.5mm diameter sheath. The needle is attached to a 2300mm long conduit with a fixed volume of 1.38ml. This is important as it acknowledges not only the volume of tracer to be used for luminal priming but the volume of 0.9% NaCl follow-through required following tracer administration to optimise tracer delivery and deposition.
C. 0.5ml of Tc-99m nano colloid reconstituted into 1.4mls is to be injected in the submucosal plane. Injection of this volume should not impede lymphatic flow.
D. After endoscopic SF localization, correct needle placement is confirmed by raising a submucosal bleb with Tc-99m directly followed by injection of the remainder of the Tc-99m. The system is flushed with 1.4 mL NaCl 0.9% post Tc-99m instillation to achieve maximal tracer administration and limit colonoscope radioactivity.
E. Crucially, the time of injection is recorded.
F. Injection of Tc-99m following localisation of the SF at the completion of the standard of care colonoscopy will add further 10 mins to the procedure time of approximately 30 minutes.
G. The tracer will be injected by Dr Krishanth Naidu.
H. A resolution clip is deployed at the site of infiltration as a further marker of SF identification on radiographic imaging.

3. Post- radio tracer placement
A. The participant is nursed within the confines of the endoscopy or operating theatre recovery suite with appropriate recovery precautions. Note is also made of reaction symptoms and signs, if any.
B. The nuclear medicine imaging suite is notified of the participants post-injection status.
C. The participant is suitably recovered prior to being transferred to the imaging suite for the SPECT-CT scan.
D. The colonoscope is submitted for appropriate cleaning and sterilization.

4. Details of SPECT-CT imaging:
A. Imaging acquisition at 1 hour following Tc-99m administration is aimed for.
B. Participant is assisted across to the gamma scanner bed
C. Time immediately prior to the commencement of the scan is recorded.
D. Dosage and radioactivity of Tc-99m is recorded in the SPECT-CT report.
E. The SPECT-CT scan will be performed under the direction of A/Prof Rob Russo ( Nuclear Medicine Physician).

5. Conclusion of visit
A. At the conclusion of the scan, participants are discharged to their residences, in accordance with standard post-endoscopic recovery and nuclear medicine protocol.
B. Formal discharge from the hospital is from the Nuclear Medicine Department. This will mirror the standard discussion plans and discussions had with a patient who has had a diagnostic scintigraphy procedure within the department. The CI (Krishanth Naidu) will be in attendance all the way through the participant’s journey to address any questions.
C. Approximately 6 hours after the injection, the radioactive tracer will be nearly all removed from your body. We would advise against caring for young children within 6 hours of the radiotracer injection. No other restrictions are necessary following discharge.
D. An investigator review (Dr Krishanth Naidu) via a follow-up phone call on Day 1, 7 and 30 from SPECT-CT completion is planned. This is to assess for delayed post-colonoscopy complications and adverse reactions. It also establishes further rapport with the research team and allows the opportunity to address concerns or issues faced by participant through the stages of participation.
Intervention code [1] 323137 0
Diagnosis / Prognosis
Intervention code [2] 324600 0
Treatment: Other
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 330771 0
Feasibility of using an endoscopically placed submucosal radio-nuclide tracer, with subsequent scintigraphy mapping using SPECT-CT technology. This will be assessed by examining or confirming:
1. Time taken for research phase of colonoscopy (using the "intubation timer" that is built in to the endoscopy operating system)
2. Submucosal instillation of the radio tracer with minimal to no spillage intraluminally (via visual inspection by researcher and confirmation on subsequent SPECT CT imaging.
3. Participant recruitment and attrition rate (via an audit of study enrolment/withdrawal logs)
4. Protocol retention rate (via an audit of study protocol diary logs)
5. Time to SPECT CT after recovery from endoscopy procedure ( via a digital stopwatch)

All measures will be assessed together as a composite primary outcome.
Timepoint [1] 330771 0
From recruitment date to day-30 following research phase of colonoscopy, instillation of radio tracer and subsequent SPECT-CT. This thus encompasses the recruitment phase, research colonoscopy phase, SPECT-CT phase and follow up phase (Day 1, Day 7 and Day 30 phone calls).
Primary outcome [2] 332989 0
Safety profile of in vivo, endoscopically placed submucosal radio-nuclide tracer, with subsequent scintigraphy mapping using SPECT-CT technology with understanding and recording of adverse reaction profile and rate. This will be assess using a study specific questionnaire via a telephone call. A clinical examination will be undertaken if clinically warranted.

Examples of known/possible adverse events include but not limited to:
1. SPECT-CT related
a. Claustrophobia in individuals with a history of anxiety in closed spaces
b. This research study involves exposure to a small amount of radiation. As part of everyday living, everyone is exposed to naturally occurring background radiation and receives a dose of about 2 millisieverts (mSv) each year. The effective dose from this study is about 3mSv and is markedly less than a multiphase CT abdomen and pelvis (~30mSv), which is regularly requested in the hospital and community setting. At the dose level used in our study, no harmful effects of radiation have been demonstrated as any effect is too small to measure. The radiation related risk is believed to be low and theoretically is less than 1 in 1000.
c. Reaction to contrast is rare but may involve:
i. Allergic reaction (e.g., rash, wheeze, difficulty breathing, fever, chest pain)
d. Per-rectal bleeding from submucosal injection

2. Colonoscopy related
a. Hole in bowel (Perforation)
i. Less than 1 in 1000 risk
b. Increased anaesthetic time
i. Slightly longer sedation time (Not expected to affect recovery time and discharge)
c. Placement of clip
i. Too deep (very rare) – causing perforation
ii. Bleeding (rare)
iii. Clip falls off
d. Pain
e. Tracer placed in an unintended layer of bowel (too deep or too shallow)
Timepoint [2] 332989 0
24hours, 7 days and 30 days following radio tracer injection and SPECT CT acquisition
Secondary outcome [1] 415454 0
Quantify the splenic drainage patterns using volumes of interest (VOI) tools that is an inherent SPECT-CT capability. All participants with image acquisition within 2 hours of radiotracer injection are considered for quantitative analysis.
Timepoint [1] 415454 0
1 hour, 2 hour and 4 hour post tracer injection using a SPECT scanner

Eligibility
Key inclusion criteria
Participants who have had a standard of care colonoscopy with normal findings and no intervention performed.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. <18 years old
2. Women lactating, pregnant, or of childbearing potential who are not willing to avoid becoming pregnant during the study.
3. Participants unable to avoid caring for young children for a minimum of 6-hours post radio tracer injection.
4. Participants with a history of colorectal surgery requiring resections.
5. Participants with a history of discontinuous colon and colostomy formation.
6. Participants undergoing an emergency colonoscopy.
7. Participants who may have any disease process that could distort the normal lymphatic drainage of the SF.
8. Participants undergoing an intervention during the colonoscopy.
9. Participants who lack capacity to provide informed consent or understand the study requirements.
10. Allergy to radio tracer or its associated constituents.
11. Participants with a history of claustrophobia.

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
The dominant lymphatic pedicle is defined by focal tracer accumulation within the mesocolon corresponding to one of the named mesenteric arterial pedicles.

Volumes of interest (VOI) will be used to delineate the amount of radioactivity for pharmacokinetics. The dominant drainage direction will be defined at 60mins post-radio tracer submucosal injection.

Only descriptive statistics will be analysed.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
16/11/2022
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
5
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 21977 0
Concord Repatriation Hospital - Concord
Recruitment postcode(s) [1] 37076 0
2139 - Concord

Funding & Sponsors
Funding source category [1] 311021 0
Hospital
Name [1] 311021 0
Concord Repatriation General Hospital
Country [1] 311021 0
Australia
Primary sponsor type
Hospital
Name
Concord Repatriation General Hospital
Address
Concord Institute of Academic Surgery
Concord Repatriation General Hospital
Building 20, Level 1
Hospital Road
Concord
NSW
2139
Australia
Country
Australia
Secondary sponsor category [1] 312508 0
None
Name [1] 312508 0
Address [1] 312508 0
Country [1] 312508 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 310568 0
Sydney Local Health District HREC - Concord Repatriation General Hospital
Ethics committee address [1] 310568 0
Ethics committee country [1] 310568 0
Australia
Date submitted for ethics approval [1] 310568 0
22/03/2022
Approval date [1] 310568 0
12/04/2022
Ethics approval number [1] 310568 0
2022/ETH00410

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 118118 0
Dr Kheng-Seong Ng
Address 118118 0
Concord Institute of Academic Surgery
Concord Repatriation General Hospital
Building 20, Level 1
Hospital Road
NSW
2139
Australia
Country 118118 0
Australia
Phone 118118 0
+61 2 9767 9992
Fax 118118 0
Email 118118 0
[email protected]
Contact person for public queries
Name 118119 0
Krishanth Naidu
Address 118119 0
Concord Institute of Academic Surgery
Concord Repatriation General Hospital
Building 20, Level 1
Hospital Road
NSW
2139
Australia
Country 118119 0
Australia
Phone 118119 0
+61 2 9767 9992
Fax 118119 0
Email 118119 0
[email protected]
Contact person for scientific queries
Name 118120 0
Kheng-Seong Ng
Address 118120 0
Concord Institute of Academic Surgery
Concord Repatriation General Hospital
Building 20, Level 1
Hospital Road
NSW
2139
Australia
Country 118120 0
Australia
Phone 118120 0
+61 2 9767 9992
Fax 118120 0
Email 118120 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Data will be collectively analysed and presented as a cohort analysis.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.