A Randomized Controlled Trial of Spermidine for the Prevention of Radiation-Induced Xerostomia in Head and Neck Squamous Cell Carcinoma (Including Nasopharyngeal Carcinoma)

Official title

A Trial of Spermidine for the Prevention of Radiation-Induced Xerostomia

Overview

This study is a single-center, double-blind, randomized controlled clinical trial with placebo as the control, aiming to evaluate the effectiveness of spermidine in preventing radiation-induced xerostomia during radiotherapy for head and neck tumors (including nasopharyngeal carcinoma).

Detailed description

This study is a single-center, double-blind, randomized controlled clinical trial with placebo as the control, aiming to evaluate the effectiveness of spermidine in preventing radiation-induced xerostomia during radiotherapy for head and neck tumors (including nasopharyngeal carcinoma).

The experimental group took spermidine capsules twice a day with meals, while the placebo group took placebo capsules twice a day with meals. The appearance and taste of the placebo and spermidine were kept the same.

The primary end point was radiation-induced xerostomia, as determined by the Xerostomia Questionnaire in which a higher score indicates worse radiation-induced xerostomia.

Interventions

• Drug Spermidine
  As a member of the polyamine family, spermidine is a trivalent cationic compound found in eukaryotic cells. It interacts with polyanions such as nucleic acids, proteins, and ATP through electrostatic binding, thereby maintaining genomic DNA stability, regulating gene transcription and translation, and modulating autophagy, apoptosis, oxidative stress, angiogenesis, and intercellular communication. Spermidine is indispensable for cell division and proliferation.
• Drug Spermidine simulants
  Patients in control group were treated with Spermidine simulants, and its use method and use time are the same as intervention group.

Primary outcome measures

• Radiation-induced xerostomia [Time frame: Radiation-induced xerostomia will be assessed weekly from the start of radiotherapy to 3 months after its completion, totaling approximately 18-19 weeks.]

Secondary outcome measures (3)

• Unstimulated salivary flow rate [Time frame: Radiation-induced xerostomia will be assessed weekly from the start of radiotherapy to 3 months after its completion, totaling approximately 18-19 weeks.]
• Quality of life (EORTC QLQ-C30) [Time frame: 1 week before radiotherapy ; at the middle of radiotherapy (3 weeks after the start of radiotherapy) ; at the end of radiotherapy(the last radiation dose received, usually 6 or 6.5 weeks) ; and 1, 2, 3 months after the end of radiotherapy.]
• Quality of life (EORTC QLQ-H&N35) [Time frame: 1 week before radiotherapy ; at the middle of radiotherapy (3 weeks after the start of radiotherapy) ; at the end of radiotherapy(the last radiation dose received, usually 6 or 6.5 weeks) ; and 1, 2, 3 months after the end of radiotherapy.]

Eligibility criteria

Inclusion criteria

• Patients with histopathologically confirmed head and neck squamous cell carcinoma (including nasopharyngeal carcinoma).
• Aged ≥18 years and ≤80 years.
• ECOG performance status score ≤2.
• Receiving radical radiotherapy or concurrent chemoradiotherapy with radiation dose >50 Gy, where: Both parotid glands receive an average dose ≥25 Gy; or one gland receives a dose ≥25 Gy and the other receives any dose.
• Blood routine parameters: hemoglobin ≥100 g/L, platelets ≥80×10⁹/L, white blood cell count ≥3.0×10⁹/L, absolute neutrophil count ≥1.5×10⁹/L.
• Signed informed consent form.

Exclusion criteria

• History of xerostomia, Sjögren's syndrome, or other known systemic diseases predisposing to dry mouth.
• Wheat allergy or gluten intolerance.
• Suspected or confirmed physical occlusion of bilateral salivary gland ducts.
• Prior history of head and neck radiotherapy.
• Use of any medications or herbal supplements that may affect salivary function within the past 30 days, or planned/final use during the study period (e.g., amifostine, cholinergic agonists \[pilocarpine, cevimeline\], certain β-adrenergic antagonists, anticholinergic drugs, or other known salivary function modifiers). If using saliva substitutes, patients must abstain from use for at least 24 hours prior to saliva and questionnaire data collection.
• Poor oral hygiene or severe periodontitis.
• Poor compliance.
• Pregnant or breastfeeding.
• Other patients deemed unsuitable by the investigator (e.g., concurrent severe comorbidities, mental disability, or severe emotional/psychiatric disorders).

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

Prevention

Study locations

China · 1 center

• West China Hospital of Sichuan University — Chengdu

Publications

• Min Y, Gao K, Liu Y, Dai L, Peng X. Oral Spermidine Supplementation Preserves Submandibular Gland Function After Radiotherapy: Mechanistic Insights and Use in a Phase II Randomized Clinical Trial. MedComm (2020). 2026 Jul 15;7(8):e70862. doi: 10.1002/mco2.70862. eCollection 2026 Aug. PMID 42460130

Identifiers

NCT: NCT07035626 · 2023-2055

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗