A Study for Assessing the Efficacy and Safety of BH4 in Radiation Enteritis

NCT05138887 | Unknown Phase 2

• 1 other identifier: WCSUH2021001
• Study Type: interventional
• Target: 366
• Locations: 1 country
• Sites: 1

Brief Summary

This present study envisaged a single-center, prospective, open-label, placebo and randomized controlled phase II clinical study to assess the efficacy and Safety of Tetrahydrobiopterin in Treating Radiation Enteritis in Gynecological Cancer Patients.

Conditions

Radiation Enteritis

Keywords

Tetrahydrobiopterin; Radiation Enteritis; Gynecological Cancer

Outcome Measures

Primary Outcomes (1)

• acute radiation-induced proctitis (ARP) incidence

  evaluated every week (according to RTOG radiation morbidity scoring criteria)

  up to 12 weeks

Secondary Outcomes (4)

• chronic radiation-induced proctitis (CRP) incidence

  up to 5 years

• progression-free survival (PFS)

  up to 5 years

• overall survival (OS

  up to 5 years

• cancer remission rate assessed by imaging

  up to 12 weeks

Other Outcomes (2)

• quality of life (QoL)

  up to 5 years

• adverse events

  up to 5 years

Study Arms (3)

placebo group

PLACEBO COMPARATOR

The placebo group was administered a vitamin tablet (Centrum) orally, once a day

Drug: Tetrahydrobiopterin

experimental group 1

EXPERIMENTAL

The experimental group 1 was administered BH4 orally, with a dose of 2mg/kg.d (If the drug dose is within the range of 51-150mg, the drug dose will be 100mg), once per day

Drug: Tetrahydrobiopterin

experimental group 2

EXPERIMENTAL

The experimental group 2 was administered BH4 orally, with a dose of 5 mg/kg.d (If the drug dose is within the range of 151-250mg, the drug dose will be 200mg, two times a day; If the drug dose is within the range of 251-350mg, the drug dose will be 300mg, three times a day)

Drug: Tetrahydrobiopterin

Interventions

Tetrahydrobiopterin DRUG

The experimental group1 was administered BH4 orally with a dose of 2 mg/kg.d, once per day, and the experimental group 2 was administered BH4 orally witha dose of 5 mg/kg.d, two times a day (If the drug dose is within the range of 151-250mg, the drug dose is 200mg) or three times a day (If the drug dose is within the range of 251-350mg, the drug dose is 300mg). The oral administration of pills was started on the same day of the first radiation treatment, and ended three months after the treatment ended.

experimental group 1; experimental group 2; placebo group

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age: ≥ 18years old female patients.
• Patients who received radical radiotherapy and chemotherapy, and who needed supplementary radiotherapy due to the prognostic risk factors for treating pathologically diagnosed gynecological malignancies (including cervical cancer, endometrial cancer, and vulvar cancer), with no pathological type restrictions.
• The Eastern Cooperative Oncology GroupPerformance Status (ECOG PS) score: 0-1.
• Expected survival ≥12 months.
• The main organs functioned normally, which meant that they met the following criteria: Hemoglobin (Hb) ≥90g/L; Absolute neutrophil count (ANC)≥1.5×109/L; Platelet count (PLT) ≥50×109/L; Total bilirubin (TBIL)\<1.5×upper limit of normal (ULN); Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST)\<2.5×ULN,for patients with liver metastasis\<5×ULN; Blood urea nitrogen (BUN) and Creatinine ratio (CR) ≤1×ULN or Endogenous creatinine clearance≥50ml/min(by Cockcroft-Gault equation).
• The subjects willingly participated inthe study, signed an informed consent form, were medication-compliant, and cooperated with the follow-ups.

You may not qualify if:

• Patients with hypertension and could not control the blood pressure within the normal range after treating with antihypertensive medications (systolic blood pressure\>140 mmHg and diastolic blood pressure\>90 mmHg).
• Patients with a history of severe cardiovascular diseases, including myocardial ischemia or myocardial infarction above grade II, poorly controlled arrhythmia (QTc interval ≥470 ms in women), grade III\~IV cardiac insufficiencyaccording to the New York Heart Association (NYHA) standards, orthe left ventricular ejection fraction (LVEF) \< 50%shown by the heart color Doppler ultrasound.
• Patients with coagulation disorders (international normalized ratio (INR) \>1.5, activated partial thromboplastin time (aPTT) \>1.5 ULN), with bleeding tendency.
• Patients with a history of psychotropic medication abuse and unable to quit, and patients with mental disorders.
• Patients participatingin another drug trial.
• Patients with concomitant diseases that seriously endangered the safety of the patient or affected the completion of the study from the investigators' opinion.
• Not suitable for enrollment in the investigators' opinion.

Sponsors & Collaborators

• West China Second University Hospital: lead

Study Sites (1)

est China Second Hospital of Sichuan University

Chengdu, Sichuan, 610016, China

RECRUITING

Related Publications (4)

• Feng Y, Feng Y, Gu L, Liu P, Cao J, Zhang S. The Critical Role of Tetrahydrobiopterin (BH4) Metabolism in Modulating Radiosensitivity: BH4/NOS Axis as an Angel or a Devil. Front Oncol. 2021 Aug 27;11:720632. doi: 10.3389/fonc.2021.720632. eCollection 2021.

  PMID: 34513700 RESULT

• Thabet NM, Rashed ER, Abdel-Rafei MK, Moustafa EM. Modulation of the Nitric Oxide/BH4 Pathway Protects Against Irradiation-Induced Neuronal Damage. Neurochem Res. 2021 Jul;46(7):1641-1658. doi: 10.1007/s11064-021-03306-0. Epub 2021 Mar 23.

  PMID: 33755856 RESULT

• Yan T, Guo S, Zhang T, Zhang Z, Liu A, Zhang S, Xu Y, Qi Y, Zhao W, Wang Q, Shi L, Liu L. Ligustilide Prevents Radiation Enteritis by Targeting Gch1/BH4/eNOS to Improve Intestinal Ischemia. Front Pharmacol. 2021 Apr 22;12:629125. doi: 10.3389/fphar.2021.629125. eCollection 2021.

  PMID: 33967762 RESULT

• Xue J, Yu C, Sheng W, Zhu W, Luo J, Zhang Q, Yang H, Cao H, Wang W, Zhou J, Wu J, Cao P, Chen M, Ding WQ, Cao J, Zhang S. The Nrf2/GCH1/BH4 Axis Ameliorates Radiation-Induced Skin Injury by Modulating the ROS Cascade. J Invest Dermatol. 2017 Oct;137(10):2059-2068. doi: 10.1016/j.jid.2017.05.019. Epub 2017 Jun 6.

  PMID: 28596000 RESULT

MeSH Terms

Interventions

sapropterin

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor

Study Record Dates

• First Submitted: October 11, 2021
• First Posted: December 1, 2021
• Study Start: March 1, 2022
• Primary Completion: October 1, 2023
• Study Completion: March 1, 2024
• Last Updated: March 2, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)