AzTrials
AzTrials

Fecal IncontinenceEarly Phase 1NCT04063293

PRP Injection Into Anal Sphincters for Fecal Incontinence

A Early Phase 1 study testing Platelet Rich Plasma in people with Fecal Incontinence, run by Istanbul Medipol University Hospital at 1 site in Turkey (Türkiye).

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
Search all trials

Trial summary

The treatment of fecal incontinence after low anterior resection is problematic, and not always able to increase quality of life. Biofeedback and rehabilitation therapies are harmless and easy to use; thus, generally selected as the initial treatment modalities, however may be effective in a small portion of patients. Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
Fecal Incontinence
What is being tested?
Platelet Rich Plasma
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
1 siteTurkey (Türkiye)
Study dates
15 May 2019to 15 Feb 2021
Phase
Early Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • incontinent patients after low anterior resection for rectal cancer

Who cannot join

  • There are 2 types of exclusion criteria
  • Patients who will not be suitable for initial tests:
  • Patients younger than 18 or older than 80
  • Pregnant or lactating women
  • Patients received pelvic radiation after the initial cancer surgery
  • Patients with local recurrence
Show all 18Show fewer
  • Patients with irresectable metastasis (patients with resectable liver and/or lung metastasis will be included after metastasectomy, but patients with peritoneal metastasis who will be candidate for peritonectomy will not be included)
  • Patients under chemotherapy
  • Patients confess incontinence prior to initial cancer surgery
  • Contraindication for PRP injection: active infection, thrombocytopenia, anemia (Hgb <10 gr/dl), allergy for buffalo thrombin
  • If the interval after the final surgery less than 12 months
  • Patient refusal
  • Patients who will be excluded according to manometer and/or endoanal ultrasound findings. Only the patients with an acceptable volume of healthy anal sphincters, an adequate reservoir capacity of neorectum and decreased sphincter strength will be included to the study after ruling out a full-thickness external sphincter tear will be the subjects of the evaluation. These patients will be excluded prior to PRP injection:
  • If manometer reveals normal resting (59-74 mm) and squeeze (124-152 mm) pressure (No clue for decreased sphincter strength)
  • If manometer reveals higher than normal volume (17-23 cc) for the first sensation, since it shows reduction of rectal sensitivity
  • If manometer reveals lessened maximum tolerable volume (MTV), since the continence may be related to the reduced volume of neorectum (For healthy volunteers the normal level of MTV is between 216 cc and 266 cc. Although normal level for neorectum after low anterior resection is not known, in a study it is accepted to be more than 60 cc as the current study [28]).
  • No or minimal external sphincter volume during: for inclusion the length, wide and volume of the external sphincter should be at least 16.1 mm, 6.8 mm and 6.3 cc, respectively (for inclusion all 3 measures should fulfilled). Although the actual minimal volume of external sphincter preventing incontinence is not indicated, in this study the minimal volume in healthy volunteers has been accepted [29,30].
  • Endoanal ultrasound examination revealing full-thickness tear in external sphincter.

Trial locations and contacts

1 site in 1 country.

Mustafa C Haksal contact

905059231965

drmustafahaksal@yahoo.com

Turkey (Türkiye)1 site, 1 recruiting

  • Istanbul Medipol University Medical School

    Istanbul, 34214

    Mustafa C Haksal, MD, 905059231965, drmustafahaksal@yahoo.com

    Mustafa C Haksal, MD

    Recruiting

Other trials in Turkey (Türkiye)

About this study

Official title: The Effect of Platelet Rich Plasma Injection Into the Anal Sphincters on Fecal Incontinence and Quality of Life in Incontinent Patients Had Treated With Low Anterior Resection for Rectal Cancer

The treatment of fecal incontinence after low anterior resection is problematic, and not always able to increase quality of life. Biofeedback and rehabilitation therapies are harmless and easy to use; thus, generally selected as the initial treatment modalities, however may be effective in a small portion of patients. More complex treatment techniques including sacral nerve stimulation decrease the severity of symptoms, however the implantation of the device is a costly, staged procedure. Little is known about the effectiveness of other techniques such as injectable substances on incontinence observed after low anterior resection. There is no study evaluating the safety and effectiveness of platelet rich plasma (PRP) injection for incontinent patients after low anterior resection.

Read the detailed description

Rectal cancer is a common problem worldwide and the standard potentially curative treatment for locally advanced disease includes radical surgery appreciating oncological principals. Sphincter-saving procedures have been practiced in order to prevent a permanent stoma; however, patients underwent low anterior resection may suffer from several problems including incontinence particularly if the initial tumor is located too close to the anal canal. The actual frequency of incontinence is still unknown because of wide variation rates in several reports ranging between 0 to 80%; and may be a long-term problem since a series has presented an incidence of 36% 10 years after surgery.

Several mechanisms may cause incontinence after low anterior resection, thus several therapeutic instruments have been described considering the underlying reason. The most reasonable suspect is probably an injury to the sphincters at the time of surgery or secondary to preoperative radiation therapy, which is a commonly used modality in order to reduce local recurrence and increase the possibility of sphincter-saving procedures with the shrinkage of the tumor. Surgery and/or (chemo)radiation may not only generate sphincter injury, but also cause nerve damage and consequent denervation of the sphincters. Internal sphincters are responsible for resting pressure. Incontinence is more often and obvious if an intersphincteric resection with a hand-sewn coloanal anastomosis is attempted, since this procedure indicates the removal of internal sphincters. Several studies have revealed that up to 20% of patients have internal sphincter injuries after low anterior resection proven with endoanal ultrasound or manometer; and diminution in size of sphincters and decrease in resting pressure are correlated with incontinence grade. Mechanical anal sphincter injury may occur during the insertion of stapler; thus, incontinence may also be observed in patients with more proximally located tumors. The effect of radiation therapy on sphincter functions is also well-known, and a prospective randomized trial has shown that radiotherapy is significantly increasing incontinence rate. Another mechanism in incontinence may be related to the reduction of the capacity of neorectum, since descending colon, which is the reconstructing organ in most cases is narrower than rectum itself. Several reservoir techniques including coloplasty, colonic j-pouch and side-to-end anastomosis have been described in order to increase pooling volume of neorectum. Some other factors including decrease in sensitivity of anal canal and anal transitional zone, alteration in rectoanal inhibitory reflex, motility dysfunction of neorectum and incomplete evacuation may separately cause incontinence or increase the severity of symptoms. Instead of a sole origin, a combination of several reasons may be present at the same time making the problem more complex and the solution tougher. The treatment of incontinence is problematic, and not always able to increase quality of life. Biofeedback and rehabilitation therapies are harmless and easy to use; thus, generally selected as the initial treatment modalities, however may be effective in a small portion of patients. More complex treatment techniques including sacral nerve stimulation decrease the severity of symptoms, however the implantation of the device is a costly, staged procedure. Little is known about the effectiveness of other techniques such as injectable substances on incontinence observed after low anterior resection. Some patients may require fecal diversion in order to achieve a better quality of life.

Platelet Rich Plasma (PRP) is a thrombocyte enriched liquid, and it increases cell proliferation and collagen formation where it is injected. Platelets activate some growth factors, cytokines and other bioactive mediators, and consequently initiate and regulate wound-healing period. PRP has been used in several chronic diseases for initiating and fastening the reconstruction phase, particularly for the tendon, muscle, ligament and articular system related injuries and inflammatory situations. The effects of PRP on symptoms and healing rate in patients with lateral epicondylitis and its superiority over bupivacaine or steroid injections have been shown in cohort and prospective randomized trials. PRP is also tested for the treatment of perianal fistula. When PRP injection is combined with mucosal advancement flap procedure, it has been shown to decrease the recurrence rate. In an animal model, PRP injection into the gastrocnemius muscle has shown to increase the strength of the muscle healing. Although it has a potential, -to the best to our knowledge- there is no study evaluating the safety and effectiveness of PRP injection for incontinent patients after low anterior resection.

Methods:

This project is a single arm, cohort study evaluating the safety and effectiveness of PRP injection into the anal sphincter on incontinence and related quality of life in incontinent patients after low anterior resection for rectal cancer. All participating patients will be informed about the protocol and PRP application, and informed consent will be obtained. The study will be run at Department of General Surgery at Istanbul Medipol University Medical School (IMU) and be completed in 24 months. Local Ethical Committee has approved the protocol (protocol number: 66291034-29) and The Scientific and Technological Research Council of Turkey (TUBITAK) has granted the study (project number: 117s133). First patient accrual is planned to happen before August 2019. For the first year, only the patients who had their previous cancer operation at IMU will be included to the study, but in case of a shortage in number of patients by the end of August 2020, the inclusion of the patients who had their initial surgeries in other institutions will be permitted.

Local Ethical Committee and governors of TUBITAK will be free to monitor the trial progress at any time. Actual status of the study will be reported to TUBITAK for observation and for the continuity of grant imbursements annually (twice during the study period) and after the finalization of data analysis and publishing. Interim analysis will not be stated, since the design has not been classified as high risk.

Being tested
Platelet Rich Plasma
Keywords
fecal incontinence, platelet rich plasma, PRP, injection
Medical subject headings
Fecal Incontinence

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Platelet Rich PlasmaBiological

    Also called PRP

    PRP injection into tha anal canal in patients underwent low anterior resection for rectal cancer

Study groups in NCT04063293
Study groupRoleWhat they receive
PRP injectionExperimentalPRP is prepared using a special device (VS-400, Genesis Comp, Korea). For each application a kit (e+ PRP, Genesis Comp, Korea) will be used. 18 cc of venous blood will be collected from the patient into the syringe with 2 cc of anticoagulant, and will be gently inverted. The sample will be slowly injected into the e+ PRP kit. The kit will be centrifuged under 1,500G for 4 minutes, which will separate the blood components into 3 different layers. The rot at the top of the kit will be pressed until the bottom of the piston will touch the red blood cell layer, and the rot will be turned clockwise to close it. The cap will be opened and the small syringe will be connected to the cap for extracting PRP. The injection will be performed in operation room under general anesthesia with either IV sedation of laryngeal mask airway (LMA) sedation. 10 cc of PRP will be directly injected in external muscles at 8 locations under the guidance of endoanal ultrasound
Receives: Biological: Platelet Rich Plasma

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Wexner fecal incontinence score change

    This scoring system cross-tabulates frequencies and different anal incontinence presentations (Gas/Liquid/Solid/Pad use/Need for lifestyle alterations) and sums the returned score to a total of 0-20 (where 0 = perfect continence and 20 = complete incontinence). Each of the incontinence presentations is graded equally.

    Measured: baseline and 6 months after PRP injection

Secondary outcomes (11)

  1. St Mark's (Vaizey) score

    analyzes different incontinence situations (solid, liquid, gas) and frequencies. Lifestyle alteration, need to wear a pad, taking constipating medicaiton and Lack of ability to defer defecation for 15 minutes. Minimum score is 0 = perfect continence; maximum score is 24 = totally incontinent.

    Measured: baseline and 6 months after PRP injection

  2. Pescatori incontinence score

    The Pescatori AI score is a grading system that combines both degree of incontinence (flatus-mucus/liquid stool/solid stool) with frequency. Incontinence ratings of A, B and C indicate AI for flatus/mucus, liquid stool, and solid stool, respectively; frequency scores of 1, 2 and 3 indicate occasional, weekly, and daily AI. A score of zero is given for normal continence. The combined score is the sum of the degree and the frequency. The minimum score is 0 and the maximum score is 6

    Measured: baseline and 6 months after PRP injection

  3. Fecal Incontinence Quality of Life Questionnaires

    a disease-specific tool, was designed to evaluate the impact of FI on four aspects of patients' QOL: lifestyle; coping behavior; depression or self perception; and level of embarrassment. The scale is composed of a total of 29 items; these items form four scales: Lifestyle (10 items), Coping/Behavior (9 items), Depression/Self-Perception (7 items), and Embarrassment (3 items).Each aspect is described as a score measured on a scale between 1 and 4, where 1 is very affected and 4 is not affected

    Measured: baseline and 6 months after PRP injection

  4. SF-36 Questionnairy

    The SF-36 has eight scaled scores; the scores are weighted sums of the questions in each section. Scores range from 0 - 100 Lower scores = more disability, higher scores = less disability Sections: Vitality, Physical functioning, Bodily pain, General health perceptions, Physical role functioning, Emotional role functioning, Social role functioning, Mental health

    Measured: baseline and 6 months after PRP injection

  5. Anal resting pressure

    Measured: baseline and 6 months after PRP injection

  6. Maximal squeeze pressure

    Measured: baseline and 6 months after PRP injection

  7. Isolated squeeze pressure

    Measured: baseline and 6 months after PRP injection

  8. Initial sensation volume

    Measured: baseline and 6 months after PRP injection

  9. Volume for defecation need

    Measured: baseline and 6 months after PRP injection

  10. Maximal tolerable volume

    Measured: baseline and 6 months after PRP injection

  11. Number of participants with PRP injection-related adverse events as assessed by CTCAE v4.0

    PRP injection safety

    Measured: up to 6 months after PRP injection

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Aug 2019
  2. Study start15 May 2019
  3. Primary completion15 Aug 2020 (estimated)
  4. Study completion15 Feb 2021 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Early Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
The injection will be performed in operation room under general anesthesia with either IV sedation of laryngeal mask airway (LMA) sedation. In case a perfect relaxation will not be achieved, then the patient will be intubated. The patient will be positioned as gynecological position. 10 cc of PRP will be directly injected in external muscles at 8 locations under the guidance of endoanal ultrasound. The final condition of the sphincters will be pictured with the device. The same surgeon (MCH) will perform all procedures. No antibiotics will be used. Local anesthetics will not be injected. If the patient will feel pain after the operation, he/she will be free to use oral painkillers. The patient will be discharged from the hospital on the same night or the day after according to the patient's desire. Patients will be questioned for possible PRP complications during the hospitalization period, and they will be asked to report anytime during the study period.
Masking
None (open label)
Enrolment
20 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04063293
Sponsor's protocol ID
IMU260702
Status last verified
Aug 2019
First submitted
15 Aug 2019
Last updated
21 Aug 2019
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: all IPD that underlie results in a publication

Publications

  • Ziv Y, Zbar A, Bar-Shavit Y, Igov I. Low anterior resection syndrome (LARS): cause and effect and reconstructive considerations. Tech Coloproctol. 2013 Apr;17(2):151-62. doi: 10.1007/s10151-012-0909-3. Epub 2012 Oct 18.

    PubMed 23076289

  • Bryant CL, Lunniss PJ, Knowles CH, Thaha MA, Chan CL. Anterior resection syndrome. Lancet Oncol. 2012 Sep;13(9):e403-8. doi: 10.1016/S1470-2045(12)70236-X.

    PubMed 22935240

  • Peeters KC, van de Velde CJ, Leer JW, Martijn H, Junggeburt JM, Kranenbarg EK, Steup WH, Wiggers T, Rutten HJ, Marijnen CA. Late side effects of short-course preoperative radiotherapy combined with total mesorectal excision for rectal cancer: increased bowel dysfunction in irradiated patients--a Dutch colorectal cancer group study. J Clin Oncol. 2005 Sep 1;23(25):6199-206. doi: 10.1200/JCO.2005.14.779.

    PubMed 16135487

  • Lundby L, Krogh K, Jensen VJ, Gandrup P, Qvist N, Overgaard J, Laurberg S. Long-term anorectal dysfunction after postoperative radiotherapy for rectal cancer. Dis Colon Rectum. 2005 Jul;48(7):1343-9; discussion 1349-52; author reply 1352. doi: 10.1007/s10350-005-0049-1.

    PubMed 15933797

  • Ridolfi TJ, Berger N, Ludwig KA. Low Anterior Resection Syndrome: Current Management and Future Directions. Clin Colon Rectal Surg. 2016 Sep;29(3):239-45. doi: 10.1055/s-0036-1584500.

    PubMed 27582649

  • Ishiyama G, Hinata N, Kinugasa Y, Murakami G, Fujimiya M. Nerves supplying the internal anal sphincter: an immunohistochemical study using donated elderly cadavers. Surg Radiol Anat. 2014 Dec;36(10):1033-42. doi: 10.1007/s00276-014-1289-3. Epub 2014 Apr 2.

    PubMed 24691518

  • Konanz J, Herrle F, Weiss C, Post S, Kienle P. Quality of life of patients after low anterior, intersphincteric, and abdominoperineal resection for rectal cancer--a matched-pair analysis. Int J Colorectal Dis. 2013 May;28(5):679-88. doi: 10.1007/s00384-013-1683-z. Epub 2013 Apr 10.

    PubMed 23571868

  • Farouk R, Duthie GS, Lee PW, Monson JR. Endosonographic evidence of injury to the internal anal sphincter after low anterior resection: long-term follow-up. Dis Colon Rectum. 1998 Jul;41(7):888-91. doi: 10.1007/BF02235373.

    PubMed 9678375

  • Hirano A, Koda K, Kosugi C, Yamazaki M, Yasuda H. Damage to anal sphincter/levator ani muscles caused by operative procedure in anal sphincter-preserving operation for rectal cancer. Am J Surg. 2011 Apr;201(4):508-13. doi: 10.1016/j.amjsurg.2009.12.016. Epub 2010 Sep 29.

    PubMed 20883975

  • Ho YH, Tsang C, Tang CL, Nyam D, Eu KW, Seow-Choen F. Anal sphincter injuries from stapling instruments introduced transanally: randomized, controlled study with endoanal ultrasound and anorectal manometry. Dis Colon Rectum. 2000 Feb;43(2):169-73. doi: 10.1007/BF02236976.

    PubMed 10696889

  • Tomita R, Igarashi S, Fujisaki S. Studies on anal canal sensitivity in patients with or without soiling after low anterior resection for lower rectal cancer. Hepatogastroenterology. 2008 Jul-Aug;55(85):1311-4.

    PubMed 18795679

  • Kim KH, Yu CS, Yoon YS, Yoon SN, Lim SB, Kim JC. Effectiveness of biofeedback therapy in the treatment of anterior resection syndrome after rectal cancer surgery. Dis Colon Rectum. 2011 Sep;54(9):1107-13. doi: 10.1097/DCR.0b013e318221a934.

    PubMed 21825890

  • Visser WS, Te Riele WW, Boerma D, van Ramshorst B, van Westreenen HL. Pelvic floor rehabilitation to improve functional outcome after a low anterior resection: a systematic review. Ann Coloproctol. 2014 Jun;30(3):109-14. doi: 10.3393/ac.2014.30.3.109. Epub 2014 Jun 23.

    PubMed 24999460

  • Tan E, Ngo NT, Darzi A, Shenouda M, Tekkis PP. Meta-analysis: sacral nerve stimulation versus conservative therapy in the treatment of faecal incontinence. Int J Colorectal Dis. 2011 Mar;26(3):275-94. doi: 10.1007/s00384-010-1119-y. Epub 2011 Jan 29.

    PubMed 21279370

  • Schwandner O. Sacral neuromodulation for fecal incontinence and "low anterior resection syndrome" following neoadjuvant therapy for rectal cancer. Int J Colorectal Dis. 2013 May;28(5):665-9. doi: 10.1007/s00384-013-1687-8. Epub 2013 Apr 5.

    PubMed 23559414

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing Platelet Rich Plasma in people with Fecal Incontinence, run by Istanbul Medipol University Hospital at 1 site in Turkey (Türkiye).

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 21 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Turkey (Türkiye). Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Mustafa C Haksal (905059231965, drmustafahaksal@yahoo.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Wexner fecal incontinence score change (time frame: baseline and 6 months after PRP injection). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04063293, which also lists 31 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Aug 2019.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in