Clinical trial NCT05525260: Limonene for Pulmonary Nodule Chemoprevention
Official title: A Randomized Phase II Trial of Limonene for Pulmonary Nodule Chemoprevention
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Pulmonary Nodules
Lead sponsor: Shanghai Jiao Tong University School of Medicine
Sponsor class: OTHER
Collaborators: name: Shanghai Chest Hospital
First posted: 2022-09-01
Enrollment: 160
Sex: FEMALE
Minimum age (years): 45
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The prevention and treatment of lung nodules involves many fields in preventive medicine and clinical medicine. A nodule is a growth or lump that may be malignant (cancer) or benign (not cancer). This study is aim to investigate the chemopreventive effect of limonene in inhibiting the occurrence/progression of ground glass pulmonary nodules. It is expected that limonene can be used as a safe and effective chemopreventive agent for preventing the development/progress of pulmonary nodules as well as expanding the indications of limonene.

Detailed description: Early prevention, early detection and early treatment of lung cancer can help reduce the incidence and improve the survival rate.Chemoprevention is known to have an important role in high-risk people because it has the potential to prevent or reverse the progression of lung cancer.Lung nodules are good targets for testing the efficacy of chemopreventive agents.So far，none of the chemopreventive agents have been shown to be effective.

Limonene is widely found in the essential oils of traditional Chinese medicine tangerine peel, green peel and other plants. Its taste is sour, sweet and pungent. It has an aromatic odor effect. Limonene Capsule, a Chinese patent medicine, has been on the market, which is suitable for the treatment of cholecystitis, cholangitis, cholelithiasis, and postoperative biliary syndrome.Preliminary studies of the research group suggest that it has a potential anti-cancer effect.

This randomized, double-blind, controlled trial studied limonene compared with placebo in treating high-risk patients with pure ground glass pulmonary nodules，so as to expand indications.

Eligibility criteria: Inclusion Criteria:

* Non-smokers (those who have smoked less than 100 cigarettes in their lifetime, including those who have never smoked in their lifetime).
* Subjects must have positive nodules detected by high-resolution CT（HRCT）: longest diameter \> 6 mm and \< 20 mm; pure ground glass nodule; according to the judgment of the clinician, follow-up can be performed, and surgical excision is not recommended for the time being; the nodules did not disappear or were not significantly reduced by more than 2 mm after six months follow-up; subjects should have at least one positive nodule when had multiple nodules.
* ECOG performance status 0-1.
* Those who accept and are willing to sign the informed consent.

Exclusion Criteria:

* Subjects with the history of autoimmune diseases and severe gastrointestinal diseases;
* Subjects suffering from malignant tumor, severe heart disease, severe liver or kidney disease currently or within the past 5 years;
* Within 6 weeks since prior herbal supplements, non-steroidal anti-inflammatory drugs, or antibiotics
* Subjects who are allergic to limonene capsules or citrus foods;
* Use of any other investigational agents at time of enrollment in the study during the three months preceding study enrollment
* Pregnant or lactating females, or those who disagreeing with contraception;
* Subjects who have a history of mental illness and cannot cooperate with this project;
* HIV-positive subjects should be excluded.
* Subjects whose organ and bone marrow function indexes exceeded the following range of normal value were excluded:

  1. Leukocytes: 3.5-9.5 109/L;
  2. Absolute neutrophil count: 1.8-6.3 109/L;
  3. Platelets: 125-350 109/L;
  4. Total bilirubin: 5.0-21.0 µmol /L;
  5. AST (SGOT)/ALT (SGPT): 0.8-1.5;
  6. Serum creatinine: 41-81 μmol/L;
* Other situations where the researcher thinks it is inappropriate to participate in this research.

Primary outcomes:
measure: Changes in the sum of longest diameters of target nodules (multiple nodules) between the drug group and the placebo group.
timeFrame: at baseline, three months and six months after administration
Secondary outcomes:
measure: Overall response rate of participants as measured by RECIST criteria between the two groups
timeFrame: at baseline, three months and six months after administration
measure: Changes in the sum of longest diameters of baseline target nodules (multiple nodules) between the drug group and the placebo group
timeFrame: at baseline and twelve months after administration
measure: Change in diameters of baseline target nodules (single nodule) detected by CT between the two groups.
timeFrame: at baseline, three months and six months after administration
measure: Change in density of baseline target nodules between the two groups.
timeFrame: at baseline, three months and six months after administration
measure: Change in the longest diameters size of baseline non-target nodules between the two groups
timeFrame: at baseline, three months and six months after administration
measure: Change in numbers of baseline non-target nodules between the two groups
timeFrame: at baseline, three months and six months after administration
measure: Change in density of baseline non-target nodules between the two groups
timeFrame: at baseline, three months and six months after administration
measure: Adverse events
timeFrame: at baseline, three months and six months after administration
measure: Value of serum miRNA
timeFrame: at baseline, three months and six months after administration
measure: Cytokine detection
timeFrame: at baseline, three months and six months after administration
measure: Plasma metabolomics
timeFrame: at baseline, three months and six months after administration
measure: Proportion of circulating blood immune cells
timeFrame: at baseline, three months and six months after administration
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Chest Hospital
state: Shanghai
Study officials:
affiliation: Shanghai Jiao Tong University School of Medicine
name: Biyun Qian, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Shanghai Chest Hospital
name: Rong Li, Doctor
role: PRINCIPAL_INVESTIGATOR
References: