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

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.

Conditions

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

Interventions

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.

OTHER

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).

Sponsors & Collaborators

• Xijing Hospital of Digestive Diseases

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

70 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2023-07-01

Primary Completion

2025-06-30

Completion

2025-12-31

Countries

• China

Study Locations