Clinical trial NCT05912712: Autologous Platelet-rich Plasma (PRP) and Thrombin Coagulum for the Topical Treatment of Rectal Mucosal Ulcers
Official title: Safety And Efficacy Study of Autologous Platelet-rich Plasma (PRP) and Thrombin Coagulum for the Topical Treatment of Rectal Mucosal Ulcers
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Ulcerative Colitis Chronic Moderate
Ulcerative Colitis Chronic Severe
Rectal Ulcer
Lead sponsor: Xijing Hospital of Digestive Diseases
Sponsor class: OTHER
First posted: 2023-06-22
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Endoscopic response rate of local treatment with autologous platelet-rich plasma gel
timeFrame: 14 weeks
Secondary outcomes:
measure: Endoscopic remission rate of local treatment with autologous platelet-rich plasma gel
timeFrame: 1 week and 14 weeks
measure: Clinical response rate of PRP-thrombin coagulum treatment on Rectal Mucosal Ulcers
timeFrame: 1 week and 14 weeks
measure: Clinical remission rate of PRP-thrombin coagulum treatment on Rectal Mucosal Ulcers
timeFrame: 1 week and 14 weeks
measure: Inflammatory parameter alteration with PRP-thrombin coagulum treatment on Rectal Mucosal Ulcers
timeFrame: 1 week, 2 weeks, 6 weeks, and 14 weeks
measure: Inflammatory response alteration with PRP-thrombin coagulum treatment on Rectal Mucosal Ulcers
timeFrame: 1 week, 2 weeks, 6 weeks, and 14 weeks
measure: Incidence of Adverse Events
timeFrame: 1 week, 2 weeks, 6 weeks, and 14 weeks
Other outcomes:
Locations:
city: Xi'an
country: China
facility: Xijing Digestive Disease
state: Shaanxi
Study officials:
References:
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.
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