Jianzhong Qushi in Chronic RRI

Official title

Jianzhong Qushi Formula for Treating Chronic Radiation Induced Proctitis : a Multicenter, Prospective, Randomized Controlled Clinical Trial

Overview

This study is a multicenter, randomized, double-blind, placebo-controlled trial. Patients diagnosed as CRP and without TCM history will be enrolled and randomly assigned to either the treatment group (receiving standard care plus Jianzhong Qushi Formula, 100 ml bid, \*28days) or the control group (receiving standard care plus placebo 100 ml bid, \*28days). All of the patients received both The primary endpoint is the clinical response rate, defined as fulfilling one of the following, RTOG grade reduction, ① RTOG/EORTC grade reduction; ② ≥1 symptom downgraded by CTCAE v5.0; ③ Symptom improvement according to TCM symptom standards .The secondary endpoints included TCM syndrome score reduction rate, LENT/SOMA score changes, changes in gut microbiota, quality of life(QoL) , etc. Totally, 168 patients (84 in each group) will be enrolled.

Detailed description

Both the treatment group and the control group are given standard treatment as recommended by the "2023 Edition of the Practice Guidelines for the Prevention and Treatment of Radiation Proctitis" or the "2018 Edition of the Expert Consensus on the Diagnosis and Treatment of Radiation Proctitis in China", such as sucralfate/steroids/loperamide according to symptoms.

① Treatment Group: Administer Jianzhong Qushi Formula, 100ml per dose, twice daily, taken before breakfast and after dinner, for a total of 28 days.

② Control Group: Administer a simulated Chinese medicine placebo, 100ml per dose, twice daily, taken before breakfast and after dinner, for a total of 28 days.

Observational medication

Jianzhong Qushi Formula (Patent No.: ZL202210097886.0) Composition:

* Monarch medicines (jun yao): Codonopsis (Dang Shen) tonifies the spleen and strengthens the body, serving as the monarch medicine.

* Minister medicines (chen yao): Atractylodes Macrocephala (Bai Zhu) is heavily used to dry dampness, transform phlegm, strengthen the spleen, and boost energy, along with Pinellia (Ban Xia) which is good at descending adverse qi and stopping vomiting, drying dampness and strengthening the spleen; both serve as the minister medicines.

* Assistant medicines (zuo yao): Poria (Fu Ling), Tangerine Peel (Chen Pi), and Amomum Tsao-ko (Cao Guo): serve to promote diuresis and reduce dampness to stop diarrhea, regulate qi to relieve abdominal pain, and dry dampness to resolve phlegm; Syzygium aromaticum (Ding Xiang) and Magnolia Officinalis (Hou Po) regulate qi and strengthen the spleen, Aucklandia Lappa (Mu Xiang) has a fragrant aroma that dries dampness, awakens the spleen, and harmonizes the middle burner, also assisting Amomum Tsao-ko and Tangerine Peel in drying dampness and resolving phlegm; Aspergillus Oryzae (Shen Qu) enters the spleen and stomach meridians, has the function of promoting digestion and appetite, and also regulates qi and resolves dampness, harmonizing the spleen and stomach; Codonopsis Pilosula (Bai Lian) regulates qi; Taraxacum Mongolicum (Pu Gong Ying) and Bletilla Stripping (Bai Ji) are combined to clear heat and detoxify, reduce swelling and disperse blood stasis, detoxify and resolve blood stasis obstruction, all serving as the assistant medicines.

* Guide medicines(shi yao): Glycyrrhiza Uralensis (Zhi Gan Cao) harmonizes all the medicines and serves as the guide medicines.

Interventions

• Drug Jianzhong Qushi Formula
  Jianzhong Qushi Formula (A Chinese traditional formula, approved by Chinese Patent, No. ZL202210097886.0)
• Drug Placebo
  A simulated Chinese medicine placebo, with similar appearance and smell to Jianzhong Qushi Formula.

Primary outcome measures

• Response rate [Time frame: 1-month, 3-month, 6-month]

Secondary outcome measures (4)

• Change of TCM syndrome scores: Calculated as (Pre-treatment Syndrome Score - Post-treatment Syndrome Score) / Pre-treatment Syndrome Score×100%. (Refer to the relevant standards in the "Guiding Principles for Clinical Research on New Traditional [Time frame: 1-month, 3-month, 6-month]
• Changes in Late Effects Normal Tissue Task Force (LENT)-Subjective, Objective, Management, Analytic (SOMA) scales [Time frame: 1-month, 3-month, 6-month]
• Changes in Quality of Life Scores [Time frame: 1-month, 3-month, 6-month]
• Changes in intestinal flora [Time frame: 1-month, 3-month, 6-month]

Eligibility criteria

Inclusion criteria

• Age 18 - 85 years old
• ECOG score ≤ 2
• Pathologically confirmed malignant tumor
• Received pelvic radiotherapy, and it has been ≥ 3 months since the end of radiotherapy ;
• Meet the diagnostic criteria for chronic radiation proctitis in the "2023 Edition of the Practice Guidelines for the Prevention and Treatment of Radiation Proctitis" or the "2023 Edition of the Expert Consensus on the Diagnosis and Treatment of Radiation Intestinal Injury in Traditional Chinese and Western Medicine in China", with an international grading of level 1 - 2
• Meet the syndrome of spleen deficiency , and the syndrome differentiation is determined according to the "2017 Edition of the Expert Consensus on the Diagnosis and Treatment of Radiation Proctitis (Intestinal Syndrome) in Traditional Chinese Medicine" formulated by the Oncology Branch of the China Association of Traditional Chinese Medicine : Basic Syndrome PRO Scale of Spleen Deficiency (meeting 2 main symptoms or 1 main symptom\* + 2 secondary symptoms#).
• Hemoglobin ≥ 100 g / L, neutrophils ≥ 1.5 × 10\^9\^ / L
• Serum creatinine ≤ 1.25 times the upper normal limit (UNL)
• Total bilirubin ≤ 1.5 times UNL, alanine aminotransferase and aspartate aminotransferase ≤ 2.5 times UNL
• The patient has signed the informed consent form
• The patient agrees to cooperate with the follow - up. \*Main symptoms included abdominal distension ,anorexia,tenesmus, unsatisfactory bowel movement and fatigue.

• Secondary symptoms included spontaneous sweating, dizziness,feeling of heaviness in the head, feeling of heaviness in the body, nausea and palpitations.

Exclusion criteria

• Other causes of enteritis cannot be ruled out
• The relevant symptoms existed before radiotherapy and did not worsen after treatment
• Allergy to more than 3 components of the Western medicine used in this study or the formula of Jianzhong Qushi Formula
• Tumor progression requiring urgent anti-tumor treatment
• Urgent surgical or endoscopic treatment is needed
• Has already entered other clinical studies targeting RRI
• Nursing or pregnant women
• Those who may interfere with the study evaluation.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Publications

• Tabaja L, Sidani SM. Management of Radiation Proctitis. Dig Dis Sci. 2018 Sep;63(9):2180-2188. doi: 10.1007/s10620-018-5163-8. PMID 29948565
• Denton A, Forbes A, Andreyev J, Maher EJ. Non surgical interventions for late radiation proctitis in patients who have received radical radiotherapy to the pelvis. Cochrane Database Syst Rev. 2002;(1):CD003455. doi: 10.1002/14651858.CD003455. PMID 11869662
• Liu L, Xiao N, Liang J. Comparative efficacy of oral drugs for chronic radiation proctitis - a systematic review. Syst Rev. 2023 Aug 22;12(1):146. doi: 10.1186/s13643-023-02294-2. PMID 37608385
• Sahebnasagh A, Ghasemi A, Akbari J, Alipour A, Lashkardoost H, Ala S, Hosseinimehr SJ, Salehifar E. Prevention of acute radiation-induced Proctitis by Aloe vera: a prospective randomized, double-blind, placebo controlled clinical trial in Pelvic Cancer patients. BMC Complement Med Ther. 2020 May 13;20(1):146. doi: 10.1186/s12906-020-02935-2. PMID 32404169
• Vanneste BG, Van De Voorde L, de Ridder RJ, Van Limbergen EJ, Lambin P, van Lin EN. Chronic radiation proctitis: tricks to prevent and treat. Int J Colorectal Dis. 2015 Oct;30(10):1293-303. doi: 10.1007/s00384-015-2289-4. Epub 2015 Jul 23. PMID 26198994
• Clarke RE, Tenorio LM, Hussey JR, Toklu AS, Cone DL, Hinojosa JG, Desai SP, Dominguez Parra L, Rodrigues SD, Long RJ, Walker MB. Hyperbaric oxygen treatment of chronic refractory radiation proctitis: a randomized and controlled double-blind crossover trial with long-term follow-up. Int J Radiat Oncol Biol Phys. 2008 Sep 1;72(1):134-143. doi: 10.1016/j.ijrobp.2007.12.048. Epub 2008 Mar 14. PMID 18342453

Identifiers

NCT: NCT06837597 · No.24/520-4800

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗