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

June 12, 2023 updated by: Jie Liang, Xijing Hospital of Digestive Diseases

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

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

60

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Shaanxi
      • Xi'an, Shaanxi, China, 710032
        • Xijing Digestive Disease

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Platelet-rich Plasma (PRP) Gel Treatment Group
Rectal 10ml platelet rich plasma gel enema + infliximab standard treatment at fixed time every day for seven consecutive days
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.
Biological: Infliximab Treatment
Patients, in every arm, all receive infliximab (300 mg iv at 0, 2, 6 weeks, and then every eight weeks).
Sham Comparator: Platelet Poor Plasma (PPP) Gel Treatment Group
Rectal 10ml PPP gel enema + infliximab standard treatment for 7 consecutive days
Biological: Infliximab Treatment
Patients, in every arm, all receive infliximab (300 mg iv at 0, 2, 6 weeks, and then every eight weeks).
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.
Active Comparator: Mesalazine Suppository Treatment Group
Patients were given 1g mesalazine suppository and infliximab daily for 7 consecutive days
Biological: Infliximab Treatment
Patients, in every arm, all receive infliximab (300 mg iv at 0, 2, 6 weeks, and then every eight weeks).
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Endoscopic response rate of local treatment with autologous platelet-rich plasma gel
Time Frame: 14 weeks
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Endoscopic remission rate of local treatment with autologous platelet-rich plasma gel
Time Frame: 1 week and 14 weeks
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
Clinical response rate of PRP-thrombin coagulum treatment on Rectal Mucosal Ulcers
Time Frame: 1 week and 14 weeks
The clinical response rate will be analyzed.
1 week and 14 weeks
Clinical remission rate of PRP-thrombin coagulum treatment on Rectal Mucosal Ulcers
Time Frame: 1 week and 14 weeks
The clinical remission rate will be analyzed.
1 week and 14 weeks
Inflammatory parameter alteration with PRP-thrombin coagulum treatment on Rectal Mucosal Ulcers
Time Frame: 1 week, 2 weeks, 6 weeks, and 14 weeks
The erythrocyte sedimentation rate will be analyzed.
1 week, 2 weeks, 6 weeks, and 14 weeks
Inflammatory response alteration with PRP-thrombin coagulum treatment on Rectal Mucosal Ulcers
Time Frame: 1 week, 2 weeks, 6 weeks, and 14 weeks
The C-reactive protein concentration will be analyzed.
1 week, 2 weeks, 6 weeks, and 14 weeks
Incidence of Adverse Events
Time Frame: 1 week, 2 weeks, 6 weeks, and 14 weeks
Adverse events will reported at the start and throughout the treatment period.
1 week, 2 weeks, 6 weeks, and 14 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Xijing Hospital of Digestive Diseases

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

July 1, 2023

Primary Completion (Estimated)

June 30, 2025

Study Completion (Estimated)

December 31, 2025

Study Registration Dates

First Submitted

May 15, 2023

First Submitted That Met QC Criteria

June 12, 2023

First Posted (Actual)

June 22, 2023

Study Record Updates

Last Update Posted (Actual)

June 22, 2023

Last Update Submitted That Met QC Criteria

June 12, 2023

Last Verified

June 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • XijingHDD-UC-PG

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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