Atorvastatin ± Aspirin in Lynch Syndrome Syndrome
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|ClinicalTrials.gov Identifier: NCT04379999|
Recruitment Status : Recruiting
First Posted : May 8, 2020
Last Update Posted : April 5, 2021
|Condition or disease||Intervention/treatment||Phase|
|Lynch Syndrome||Drug: Atorvastatin 20mg Drug: Atorvastatin 20mg AND Aspirin 325 mg||Early Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||46 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||One group receives atorvastatin 20 mg, and the other group receives atorvastatin 20 mg+ aspirin 325mg|
|Masking:||None (Open Label)|
|Official Title:||Impact of Atorvastatin ± Aspirin on Colorectal Biomarkers in Patients With Lynch Syndrome: a Pilot Study|
|Actual Study Start Date :||September 10, 2018|
|Estimated Primary Completion Date :||September 1, 2022|
|Estimated Study Completion Date :||September 10, 2023|
Active Comparator: Atorvastatin
Atorvastatin (LIPITOR) 20 milligram tablet daily for 6 weeks
Drug: Atorvastatin 20mg
No history of colorectal cancer and no colorectal adenomas within 5 years.
Other Name: Lipitor 20mg
Active Comparator: Atorvastatin and Aspirin
Atorvastatin (LIPITOR) 20 milligram tablet and Aspirin 325 mg tablet daily for 6 weeks
Drug: Atorvastatin 20mg AND Aspirin 325 mg
History of colorectal cancer and/or history of colorectal adenomas within 5 years.
Other Name: Lipitor 20mg AND Aspirin 325mg
- Proliferation (Ki-67) and apoptosis (active caspase 3) by immunohistochemical staining [ Time Frame: Changes from baseline to 6 weeks ]Effect of Atorvastatin or/and Aspirin on normal colonic proliferation and apoptosis will be evaluated by comparing of immunohistochemical staining of Ki-67 and active caspase 3 using formalin-fixed paraffin-embedded biopsies collected before and at the 6 weeks of drug treatments. Number of positive cells and total number of evaluated cells will be collected for both assays. Data of cells with positive Ki-67 or active caspase 3 will be expressed as % of positive cells (# positive cells/#total evaluated cells x 100). Statistical analyses will be performed to compare the difference between baseline and 6-weeks data.
- Genome-wide expression analyses using RNA-Seq [ Time Frame: Changes from baseline to 6 weeks ]Effect of Atorvastatin or/and Aspirin on gene expressions in normal colonic epithelial cells will be analyzed using RNA-Seq. Total RNA will be extracted from frozen biopsies. RNASeq libraries will be generated and sequenced on an Illumina platform and analyzed. Differential expression between samples at baseline and 6-weeks of drug treatment will be assessed for statistical significance. Genes with false discovery rat ≤ 0.05 and a fold-change ≥ 2 will be considered significant.
- Rate of adherence of healthy patients with Lynch Syndrome to a 6-week of the treatment regimen (atorvastatin ± aspirin). [ Time Frame: 6 weeks ]Medication Adherence to the 6-week course of Atorvastatin or/and Aspirin preventive therapy will be assessed by one question in the follow -up survey which participants complete at the end of the study :"Over 6 weeks of preventive therapy, how many Atorvastatin/Aspirin pills did you forget to take?" In addition, participants will be asked to return medication bottle(s) with or without pills. RA will count pills and record number of missing pills in the system.
- Frequency of adverse events among patients administered atorvastatin ± aspirin for 6 weeks [ Time Frame: 6 weeks ]The adverse event assessment form is used to collect initial and follow-up information for non-serious and serious adverse events for patients participating in the study. Participants are contacted by RA every two weeks to assess side effects and toxicity. A grading scale from 1 to 5 (1-mild, 2-moderate, 3-severy, 4-life-threatining, 5- death related to AE) and causality (1-unrelated, 2-unlikly, 3-possible, 4-probable, 5-definite, NA- not assessed) are recorded for each adverse event (AE) term. Each AE is reviewed by principal investigator and entered into patient's electronic medical record (EMR)
- Acceptability of the pilot study intervention and the willingness of the subject to participate in a similar larger study. [ Time Frame: 6 weeks ]Acceptability of the study approach 6 Likert-type items (7 point scale) will assess participants' perceptions of various aspects of the study design as a measure of whether changes need to be made to the study methods or design prior to a larger multi-institutional trial. Participants' scores will be summed and a mean score generated. Mean scores > 4 will be considered in the acceptable range. Our threshold target is 75% of participants with a mean score in the acceptable range.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04379999
|Contact: Yana Chertock, MAfirstname.lastname@example.org|
|United States, Pennsylvania|
|Fox Chase Cancer Center||Recruiting|
|Philadelphia, Pennsylvania, United States, 19111|
|Contact: Yana Chertock, MA 215-214-3216 email@example.com|
|Contact: Michael Hall, MD, MS 215-728-2791 firstname.lastname@example.org|
|Principal Investigator: Michael J Hall, MD, MS|
|Sub-Investigator: Margie L Clapper, PhD|
|Sub-Investigator: Minhhuyen T Nguyen, MD,AGAF,FACP|
|Sub-Investigator: Harry S Cooper, MD|
|Sub-Investigator: Wen-Chi L Chang, PhD|
|Principal Investigator:||Michael J Hall, MD, MS||Fox Chase Cancer Center|