Autologous Platelet-rich Plasma (PRP) and Thrombin Coagulum for the Topical Treatment of Rectal Mucosal Ulcers

Ulcerative Colitis Chronic Moderate Clinical Trial

Official title:

Safety And Efficacy Study of Autologous Platelet-rich Plasma (PRP) and Thrombin Coagulum for the Topical Treatment of Rectal Mucosal Ulcers

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05912712
• Other study ID #: XijingHDD-UC-PG
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: July 1, 2023
• Est. completion date: December 31, 2025

Study information

• Verified date: June 2023
• Source: Xijing Hospital of Digestive Diseases
• Contact: Yanting Shi, M.S.
• Phone: +86-029-84771535
• Email: yantings[@]fmmu.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Ulcerative colitis (UC) is a chronic persistent inflammatory disease. The lesions are mainly confined to the large intestine and continuously affect the rectum and part or all of the colon. Its histological characteristics are diffuse neutrophil infiltration in the lamina propria of the colon mucosa, mucosal erosion, ulcer, cryptitis, and crypt abscess. The most common clinical manifestations are abdominal pain, diarrhea, and bloody mucopurulent stool, accompanied by extraintestinal manifestations such as mouth, skin, joints, and eyes. Severe lesions can be complicated by toxic megacolon, intestinal perforation, lower gastrointestinal hemorrhage, intraepithelial neoplasia, and cancer, so surgical treatment is necessary. Studies have reported that UC patients have a 10-year cumulative recurrence risk of 70%-80%, nearly 50% of patients require UC-related hospitalization, and the 5-year risk of re-hospitalization is ~ 50%. The 5-year and 10-year cumulative risk of patients undergoing colectomy is 10%-15%, which dramatically endangers the health of patients and reduces the quality of life of patients.

Currently, the commonly used medical treatment drugs for UC patients include 5-aminosalicylic acid, topical and systemic glucocorticoids, immunomodulators, anti-tumor necrosis factor drugs, and other biological agents. The most commonly used optimization methods are drug escalation therapy and combining drugs with different mechanisms. The real-world data results of an initial population-based cohort study from six Asian countries showed that the endoscopic mucosal healing rate of patients with ulcerative colitis in the first year of diagnosis was 38.2%, and the histological mucosal healing rate was 23.1%. It can be expected that the mucosal healing rate of patients with moderate to severe UC may be lower. Long-term chronic recurrent diseases may lead to poorer quality of life, extended hospital stays, heavier financial burdens, and more physical and mental pain. Therefore, optimizing the treatment plan for patients with moderate to severe UC needs more exploration and research.

Autologous Platelet-rich plasma (A-PRP) is A platelet-rich concentrate obtained by centrifugation of whole blood. As a concentrated source of autologous platelets, they contain a large number of Growth factors (GF) and cytokines, such as platelet-derived Growth factor (PDGF), transforming growth factor β(TGF-β), vascular endothelial growth factor (VEGF) and epithelial growth factor (EGF), which regulate cell function. Such as attachment, macrophage migration, proliferation, and differentiation, promote extracellular matrix accumulation and ultimately improve tissue healing and regeneration. At the same time, A-PRP has A lower risk of adverse reactions such as immune rejection and allergy due to its isolation from autologous blood.

After PRP is induced by activators such as calcium and thrombin, activated platelets degranulate immediately and secrete multiple high concentrations of growth factors. 70% of the growth factors can be released within 10 minutes of activation, and more than 95% can be released within the first hour. Platelet-rich Gel (PG), which can embed growth factors to improve clinical efficacy, keeps platelets and their release products in the target wound area and promotes healing.

Although the safety and efficacy of PRP still need to be fully confirmed by large-scale clinical trials, its sound effect has been verified in many clinical practices and basic scientific research in cell culture and animal models. At present, it mainly includes the treatment of oral and maxillofacial external, musculoskeletal system, plastic skin, and chronic wounds (such as pressure ulcers, venous leg ulcers, diabetic foot ulcers, etc.). They can be mixed into bone grafts, sprayed on soft tissue surfaces as a biofilm, or made into eye drops.

The use of PRP in intestinal mucosal ulcers has rarely been reported. There are no prospective randomized studies of its clinical use in patients with ulcerative colitis. Therefore, we planned to conduct a prospective, randomized, double-blind, controlled clinical trial to investigate the efficacy and safety of repeated treatment with autologous platelet-rich plasma gel on an intestinal mucosal ulcer in patients with moderate to severe UC involving the rectum in Xijing Hospital, China IBD Regional Center. To provide a new option for remission induction therapy in patients with moderate to severe ulcerative colitis.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 60
• Est. completion date: December 31, 2025
• Est. primary completion date: June 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

1. Platelet =150×10^9g/L, hemoglobin =60g/L;

2. Patients with ulcerative colitis were diagnosed according to the diagnostic criteria of ulcerative colitis in the 2018 China's National consensus on the diagnosis and treatment of inflammatory bowel disease;

3. Patients with moderate to severe ulcerative colitis involving the rectum or refractory distal rectal ulcerative colitis (modified Mayo score =6 and endoscopic Mayo score =2);

4. Patients with ulcerative colitis who were initially treated with infliximab (according to a regular intravenous infusion schedule of 0w, 2w, 6w, and then every 8w);

5. Patients who were able and willing to adhere to the study protocol provided signed, dated, written informed consent.

Exclusion Criteria:

1. Patients with platelet-related bleeding diseases (such as Henoch-Schonlein purpura, coagulopathy, primary/secondary thrombocytopenia, etc.);

2. Medications with anticoagulant effects such as nonsteroidal anti-inflammatory drugs, heparin, coumarin, warfarin, aspirin, etc. (acetaminophen was used to treat discomfort during the study period);

3. Patients using mesalazine enema solution during treatment;

4. Patients with active infection of intestinal or other extra-intestinal organs (hepatitis, active tuberculosis, etc.);

5. Patients with known hypersensitivity to calcium gluconate and thrombin

6. Patients who may require immediate surgical treatment;

7. Pregnant or nursing mothers;

8. Patients with severe liver and kidney dysfunction, heart failure or other serious systemic diseases;

9. Any conditions that prevent the completion of the study or interfere with the analysis of the study results, including drug or alcohol abuse history, smoking abstinence, mental illness or poor compliance, and clear immune system (including HIV infection), blood system or cancer related diseases;

10. Patients who withdraw consent;

11. Patients enrolled in other clinical trials within 3 months prior to screening.

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Rectal Ulcer
• Ulcer
• Ulcerative Colitis Chronic Moderate
• Ulcerative Colitis Chronic Severe

Intervention

Other:
• Autologous Platelet-rich Plasma (PRP) and Thrombin Coagulum Treatment
10 mL PRP and thrombin coagulum gel was administered every night for seven consecutive days by the same IBD specialist. Before the intervention, the patients had to defecate. The prepared PRP gel was injected into the external opening of the rectum using the same syringe, and the patient was kept in the Trendelenburg position to ensure that the therapeutic drug remained in place under gravity. The normal supine position was returned after 15 minutes to minimize PRP leakage. The outflow was observed, and the amount of outflow was recorded.
• Autologous Platelet-poor Plasma (PPP) and Thrombin Coagulum Treatment
10 mL PPP and thrombin coagulum gel was administered every night for seven consecutive days by the same IBD specialist. Before the intervention, the patients had to defecate. The prepared PPP gel was injected into the external opening of the rectum using the same syringe, and the patient was kept in the Trendelenburg position to ensure that the therapeutic drug remained in place under gravity. The normal supine position was returned after 15 minutes to minimize PPP leakage. The outflow was observed, and the amount of outflow was recorded.

Drug:
• Mesalazine Suppository Treatment
For patients receiving mesalazine suppositories, the intervention was inserted through the anus with a disposable sanitary finger to the point of slight loss of resistance. To facilitate intervention, moisturize with water or cream. If the drug drains within 10 minutes, it should be re-inserted. The swelling at the local injection site on each group's intervention day was recorded.

Biological:
• Infliximab Treatment
Patients, in every arm, all receive infliximab (300 mg iv at 0, 2, 6 weeks, and then every eight weeks).

Locations

Country	Name	City	State
China	Xijing Digestive Disease	Xi'an	Shaanxi

Sponsors (1)

Lead Sponsor	Collaborator
Xijing Hospital of Digestive Diseases

Country where clinical trial is conducted

China, 

References & Publications (9)

Al-Hamed FS, Abu-Nada L, Rodan R, Sarrigiannidis S, Ramirez-Garcialuna JL, Moussa H, Elkashty O, Gao Q, Basiri T, Baca L, Torres J, Rancan L, Tran SD, Lordkipanidze M, Kaartinen M, Badran Z, Tamimi F. Differences in platelet-rich plasma composition influence bone healing. J Clin Periodontol. 2021 Dec;48(12):1613-1623. doi: 10.1111/jcpe.13546. Epub 2021 Sep 27. — View Citation

Fumery M, Singh S, Dulai PS, Gower-Rousseau C, Peyrin-Biroulet L, Sandborn WJ. Natural History of Adult Ulcerative Colitis in Population-based Cohorts: A Systematic Review. Clin Gastroenterol Hepatol. 2018 Mar;16(3):343-356.e3. doi: 10.1016/j.cgh.2017.06.016. Epub 2017 Jun 16. — View Citation

Hesseler MJ, Shyam N. Platelet-rich plasma and its utility in medical dermatology: A systematic review. J Am Acad Dermatol. 2019 Sep;81(3):834-846. doi: 10.1016/j.jaad.2019.04.037. Epub 2019 Apr 19. — View Citation

Lee JH, Kim MJ, Ha SW, Kim HK. Autologous Platelet-rich Plasma Eye Drops in the Treatment of Recurrent Corneal Erosions. Korean J Ophthalmol. 2016 Apr;30(2):101-7. doi: 10.3341/kjo.2016.30.2.101. Epub 2016 Mar 25. — View Citation

Lee JW, Kwon OH, Kim TK, Cho YK, Choi KY, Chung HY, Cho BC, Yang JD, Shin JH. Platelet-rich plasma: quantitative assessment of growth factor levels and comparative analysis of activated and inactivated groups. Arch Plast Surg. 2013 Sep;40(5):530-5. doi: 10.5999/aps.2013.40.5.530. Epub 2013 Sep 13. — View Citation

Leung CM, Tang W, Kyaw M, Niamul G, Aniwan S, Limsrivilai J, Wang YF, Ouyang Q, Simadibrata M, Abdullah M, Ong DE, Yu HH, Zhang J, Ching J, Wu JCY, Chan FKL, Sung JJY, Ng SC. Endoscopic and Histological Mucosal Healing in Ulcerative Colitis in the First Year of Diagnosis: Results from a Population-based Inception Cohort from Six Countries in Asia. J Crohns Colitis. 2017 Dec 4;11(12):1440-1448. doi: 10.1093/ecco-jcc/jjx103. — View Citation

Marx RE. Platelet-rich plasma: evidence to support its use. J Oral Maxillofac Surg. 2004 Apr;62(4):489-96. doi: 10.1016/j.joms.2003.12.003. No abstract available. — View Citation

Nikolidakis D, Jansen JA. The biology of platelet-rich plasma and its application in oral surgery: literature review. Tissue Eng Part B Rev. 2008 Sep;14(3):249-58. doi: 10.1089/ten.teb.2008.0062. — View Citation

Shao S, Pan R, Chen Y. Autologous Platelet-Rich Plasma for Diabetic Foot Ulcer. Trends Endocrinol Metab. 2020 Dec;31(12):885-890. doi: 10.1016/j.tem.2020.10.003. Epub 2020 Nov 13. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Endoscopic response rate of local treatment with autologous platelet-rich plasma gel	Endoscopic response rate of local treatment with autologous platelet-rich plasma gel in patients with moderate to severe ulcerative colitis involving the rectum.	14 weeks
Secondary	Endoscopic remission rate of local treatment with autologous platelet-rich plasma gel	Endoscopic remission rate of local treatment with autologous platelet-rich plasma gel in patients with moderate to severe ulcerative colitis involving the rectum.	1 week and 14 weeks
Secondary	Clinical response rate of PRP-thrombin coagulum treatment on Rectal Mucosal Ulcers	The clinical response rate will be analyzed.	1 week and 14 weeks
Secondary	Clinical remission rate of PRP-thrombin coagulum treatment on Rectal Mucosal Ulcers	The clinical remission rate will be analyzed.	1 week and 14 weeks
Secondary	Inflammatory parameter alteration with PRP-thrombin coagulum treatment on Rectal Mucosal Ulcers	The erythrocyte sedimentation rate will be analyzed.	1 week, 2 weeks, 6 weeks, and 14 weeks
Secondary	Inflammatory response alteration with PRP-thrombin coagulum treatment on Rectal Mucosal Ulcers	The C-reactive protein concentration will be analyzed.	1 week, 2 weeks, 6 weeks, and 14 weeks
Secondary	Incidence of Adverse Events	Adverse events will reported at the start and throughout the treatment period.	1 week, 2 weeks, 6 weeks, and 14 weeks