Limonene for Pulmonary Nodule Chemoprevention
Primary Purpose
Pulmonary Nodules
Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Limonene capsule
Limonene capsules(Placebo)
Sponsored by
About this trial
This is an interventional prevention trial for Pulmonary Nodules
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:
- Leukocytes: 3.5-9.5 109/L;
- Absolute neutrophil count: 1.8-6.3 109/L;
- Platelets: 125-350 109/L;
- Total bilirubin: 5.0-21.0 µmol /L;
- AST (SGOT)/ALT (SGPT): 0.8-1.5;
- Serum creatinine: 41-81 μmol/L;
- Other situations where the researcher thinks it is inappropriate to participate in this research.
Sites / Locations
- Shanghai Chest HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Limonene capsules(marketed product in China)
Limonene capsules(Placebo)
Arm Description
Limonene capsules(marketed product in China) donate by pharmaceutical company.
Same smell, color and shape as limonene capsules(marketed product in China), without limonene in capsules.
Outcomes
Primary Outcome Measures
Changes in the sum of longest diameters of target nodules (multiple nodules) between the drug group and the placebo group.
Difference in the sum of longest diameters of target nodules
Secondary Outcome Measures
Overall response rate of participants as measured by RECIST criteria between the two groups
Difference in the overall response rate of participants
Changes in the sum of longest diameters of baseline target nodules (multiple nodules) between the drug group and the placebo group
Difference in the sum of longest diameters of target nodules
Change in diameters of baseline target nodules (single nodule) detected by CT between the two groups.
Difference in the longest diameters of baseline target nodules
Change in density of baseline target nodules between the two groups.
Difference in density of baseline target nodules
Change in the longest diameters size of baseline non-target nodules between the two groups
Difference in the longest diameters of baseline non-target nodules
Change in numbers of baseline non-target nodules between the two groups
Difference in numbers of baseline non-target nodules
Change in density of baseline non-target nodules between the two groups
Difference in density of baseline non-target nodules
Adverse events
Incidence of adverse events
Value of serum miRNA
Value of serum miRNA
Cytokine detection
Value of cytokine detection
Plasma metabolomics
Analysis of plasma metabolomics
Proportion of circulating blood immune cells
Analysis of the proportion of circulating blood immune cells
Full Information
NCT ID
NCT05525260
First Posted
August 9, 2022
Last Updated
February 2, 2023
Sponsor
Shanghai Jiao Tong University School of Medicine
Collaborators
Shanghai Chest Hospital
1. Study Identification
Unique Protocol Identification Number
NCT05525260
Brief Title
Limonene for Pulmonary Nodule Chemoprevention
Official Title
A Randomized Phase II Trial of Limonene for Pulmonary Nodule Chemoprevention
Study Type
Interventional
2. Study Status
Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 2023 (Anticipated)
Primary Completion Date
February 2024 (Anticipated)
Study Completion Date
December 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Shanghai Jiao Tong University School of Medicine
Collaborators
Shanghai Chest Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Nodules
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
160 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Limonene capsules(marketed product in China)
Arm Type
Active Comparator
Arm Description
Limonene capsules(marketed product in China) donate by pharmaceutical company.
Arm Title
Limonene capsules(Placebo)
Arm Type
Placebo Comparator
Arm Description
Same smell, color and shape as limonene capsules(marketed product in China), without limonene in capsules.
Intervention Type
Drug
Intervention Name(s)
Limonene capsule
Other Intervention Name(s)
DAN LENING capsule
Intervention Description
Citrus foods rich in D-limonene were forbiden 2 days before taking the drug (washout period), which was maintained after taking the drug.Limonene capsules group and placebo group were used for treatment. The random number is generated by the central randomization system. All the recruiters were divided into placebo control group and limonene capsule administration group. The numbers will be assigned according to random numbers. In this study, qualified subjects were randomly assigned to the treatment group and the placebo control group at a ratio of 1:1. The drug was administered for 12 weeks, 3 times a day, 5 capsules each time.
Intervention Type
Drug
Intervention Name(s)
Limonene capsules(Placebo)
Other Intervention Name(s)
Placebo
Intervention Description
Limonene capsules(Placebo)
Primary Outcome Measure Information:
Title
Changes in the sum of longest diameters of target nodules (multiple nodules) between the drug group and the placebo group.
Description
Difference in the sum of longest diameters of target nodules
Time Frame
at baseline, three months and six months after administration
Secondary Outcome Measure Information:
Title
Overall response rate of participants as measured by RECIST criteria between the two groups
Description
Difference in the overall response rate of participants
Time Frame
at baseline, three months and six months after administration
Title
Changes in the sum of longest diameters of baseline target nodules (multiple nodules) between the drug group and the placebo group
Description
Difference in the sum of longest diameters of target nodules
Time Frame
at baseline and twelve months after administration
Title
Change in diameters of baseline target nodules (single nodule) detected by CT between the two groups.
Description
Difference in the longest diameters of baseline target nodules
Time Frame
at baseline, three months and six months after administration
Title
Change in density of baseline target nodules between the two groups.
Description
Difference in density of baseline target nodules
Time Frame
at baseline, three months and six months after administration
Title
Change in the longest diameters size of baseline non-target nodules between the two groups
Description
Difference in the longest diameters of baseline non-target nodules
Time Frame
at baseline, three months and six months after administration
Title
Change in numbers of baseline non-target nodules between the two groups
Description
Difference in numbers of baseline non-target nodules
Time Frame
at baseline, three months and six months after administration
Title
Change in density of baseline non-target nodules between the two groups
Description
Difference in density of baseline non-target nodules
Time Frame
at baseline, three months and six months after administration
Title
Adverse events
Description
Incidence of adverse events
Time Frame
at baseline, three months and six months after administration
Title
Value of serum miRNA
Description
Value of serum miRNA
Time Frame
at baseline, three months and six months after administration
Title
Cytokine detection
Description
Value of cytokine detection
Time Frame
at baseline, three months and six months after administration
Title
Plasma metabolomics
Description
Analysis of plasma metabolomics
Time Frame
at baseline, three months and six months after administration
Title
Proportion of circulating blood immune cells
Description
Analysis of the proportion of circulating blood immune cells
Time Frame
at baseline, three months and six months after administration
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
45 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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:
Leukocytes: 3.5-9.5 109/L;
Absolute neutrophil count: 1.8-6.3 109/L;
Platelets: 125-350 109/L;
Total bilirubin: 5.0-21.0 µmol /L;
AST (SGOT)/ALT (SGPT): 0.8-1.5;
Serum creatinine: 41-81 μmol/L;
Other situations where the researcher thinks it is inappropriate to participate in this research.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ziyi Sheng, Master
Phone
22200000
Ext
5452
Email
shxkcru@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Biyun Qian, Doctor
Organizational Affiliation
Shanghai Jiao Tong University School of Medicine
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Rong Li, Doctor
Organizational Affiliation
Shanghai Chest Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Shanghai Chest Hospital
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200030
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sheng Zi Yi, Master
Phone
22200000
Ext
5452
Email
shxkcru@163.com
12. IPD Sharing Statement
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Limonene for Pulmonary Nodule Chemoprevention
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