Abnormal Food Timing and Circadian Dyssynchrony in Alcohol Induced Colon Carcinogenesis

NCT ID: NCT03955510

Last Updated: 2025-10-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

NA

Total Enrollment

12 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-07-31

Study Completion Date

2026-05-31

Brief Summary

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The purpose of this study is to study the impact of Western lifestyle, including moderate alcohol consumption and delayed eating patterns on studying individuals' susceptibility to colorectal cancer. This study aims to increase our ability to identify individuals at risk for colorectal cancer in the future.

Each subject will experience four conditions (each for one week in duration with a week +/- 2 days wash-out in between): (1) "right-time eating" / no alcohol, (2) "right-time eating" / with alcohol, (3) "delayed-eating" / no alcohol, (4) "delayed-eating" / with alcohol. The order of experiments will be randomized \[concealed randomization\]. All subjects will undergo unprepped sigmoidoscopy after each week of intervention. In Aim 2, all subjects will have an option to undergo a 24h circadian assessment in the Biological Rhythms Research Lab after each week of intervention. The Investigator will assess (i) central circadian rhythms by collecting hourly salivary samples for melatonin assays and (ii) peripheral rhythm in the intestinal tract by buccal swabs once every 2h (12 time points) as well as by rectal sampling twice (every 12 hr). For Aim 3, sigmoidoscopy without sedation will be used to obtain colonic samples as the safe method compared to colonoscopy, which has some small but finite risks associated with the procedure (e.g, bleeding or perforation) as well as sedation.

Detailed Description

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Colorectal cancer (CRC) is the second leading cause of cancer mortality in the US. CRC's risk is closely linked to the modern lifestyle. Alcohol is commonly used in our society and is an established risk factor for both pre-cancerous (polyp) and cancerous lesions of the colon. However this knowledge has not been translated to our current risk stratifications for CRC as the process of alcohol-induced carcinogenesis is not predictable. Mucosal inflammation is a well-established mechanism that mediates the effect of alcohol induced tissue injury in the intestine. Inflammation also plays a crucial role in pathogenesis of CRC. Factors that promote a pro-tumorigenic inflammatory state in the setting of alcohol are unknown. Since CRC occurs only in a small subset of alcohol user, alcohol alone may not be sufficient to start the neoplastic process and additional cofactors are required. One such factor is circadian dysrhythmia that is another modern lifestyle habit, shown to be associated with an increased risk of CRC. Further, previous research has shown that disruption of circadian rhythm exacerbates alcohol-induced intestinal inflammation. The Investigator hypothesize that altered circadian rhythms due to "wrong-time" eating (abnormal eating) are an important determinant in alcohol induced mucosal inflammation and carcinogenesis. Our preliminary data supports our hypothesis and shows that abnormal eating patterns accelerate alcohol-induced polyposis in a mouse model of CRC. Each subject will experience four conditions (each for one week in duration with a week +/- 2 days wash-out in between): (1) "right-time eating" / no alcohol, (2) "right-time eating" / with alcohol, (3) "delayed-eating" / no alcohol, (4) "delayed-eating" / with alcohol. The order of experiments will be randomized \[concealed randomization\]. All subjects will undergo unprepped sigmoidoscopy after each week of intervention. In Aim 2, all subjects will have an option to undergo a 24h circadian assessment in the Biological Rhythms Research Lab after each week of intervention. The Investigator will assess (i) central circadian rhythms by collecting hourly salivary samples for melatonin assays and (ii) peripheral rhythm in the intestinal tract by buccal swabs once every 2h (12 time points) as well as by rectal sampling twice (every 12 hr). For Aim 3, sigmoidoscopy without sedation will be used to obtain colonic samples as the safe method compared to colonoscopy, which has some small but finite risks associated with the procedure (e.g, bleeding or perforation) as well as sedation.

Conditions

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Colorectal Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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"Right-time eating" / no alcohol

"Right-time eating" means breakfast before 8am, lunch before 1 pm and dinner before 6pm. Subjects will be asked to stick to this eating schedule for 1 week. Subjects will be asked to not drink alcohol for 1 week. Subjects will randomly be assigned to each eating pattern during the study period.

Group Type OTHER

Right time eating

Intervention Type OTHER

"Right-time eating" means breakfast before 8am, lunch before 1 pm and dinner before 6pm. Subjects will be asked to stick to this eating schedule for 1 week. Subjects will randomly be assigned to each eating pattern during the study period. Each subject will be required to do this intervention twice during the study period. One time they will have right time eating with alcohol , the second time the will have this intervention without alcohol.

Sigmoidoscopy

Intervention Type PROCEDURE

Subjects will undergo unprepped sigmoidoscopy to collect tissue and stool sample at each intervention visits (visit 2, 3, 4, and 5). Flexible sigmoidoscopy will not require any colon cleansing and it will be very limited to the most distal (closest to the end of the anus) 20 centimeters (approximately 8 inches) of the colon and thus will be far less uncomfortable than the routine flexible sigmoidoscopy.

Optional 24h circadian assessment in the Biological Rhythms lab

Intervention Type PROCEDURE

Subjects may choose to participate in the 24 hour circadian assessment in the Biological Rhythms Research Lab. During this assessment, a saliva sample will be taken every hour, a mouth swab will be done every 2 hours, and rectal swab will be done twice (every 12 hours). Subjects will be kept awake in dim light on a recliner chair. Subjects can watch a television with dimmed light. Subjects will be provided with food and drink during the assessment.

If subjects choose this intervention they will be asked to complete 4 assessment during the course of the study period.

"Right-time eating" / with alcohol

"Right-time eating" means breakfast before 8am, lunch before 1 pm and dinner before 6pm. Subjects will be asked to stick to this eating schedule for 1 week. Subjects will randomly be assigned to each eating pattern during the study period. Moderate alcohol drinking means 0.3-0.5 g/kg alcohol daily, which will be not more than 2 glasses of wine depending on subject's weight. Alcohol will always be consumed in the evening with food or after food (e.g., dinner). The timing of alcohol consumption will be consistent for each individual. Subjects will be provided with red wine for the 1 alcohol intervention week. The order of conditions will be random.

Group Type OTHER

Right time eating

Intervention Type OTHER

"Right-time eating" means breakfast before 8am, lunch before 1 pm and dinner before 6pm. Subjects will be asked to stick to this eating schedule for 1 week. Subjects will randomly be assigned to each eating pattern during the study period. Each subject will be required to do this intervention twice during the study period. One time they will have right time eating with alcohol , the second time the will have this intervention without alcohol.

Sigmoidoscopy

Intervention Type PROCEDURE

Subjects will undergo unprepped sigmoidoscopy to collect tissue and stool sample at each intervention visits (visit 2, 3, 4, and 5). Flexible sigmoidoscopy will not require any colon cleansing and it will be very limited to the most distal (closest to the end of the anus) 20 centimeters (approximately 8 inches) of the colon and thus will be far less uncomfortable than the routine flexible sigmoidoscopy.

Optional 24h circadian assessment in the Biological Rhythms lab

Intervention Type PROCEDURE

Subjects may choose to participate in the 24 hour circadian assessment in the Biological Rhythms Research Lab. During this assessment, a saliva sample will be taken every hour, a mouth swab will be done every 2 hours, and rectal swab will be done twice (every 12 hours). Subjects will be kept awake in dim light on a recliner chair. Subjects can watch a television with dimmed light. Subjects will be provided with food and drink during the assessment.

If subjects choose this intervention they will be asked to complete 4 assessment during the course of the study period.

Alcohol

Intervention Type OTHER

Moderate alcohol drinking means 0.5 g/kg alcohol daily, which will be not more than 2 glasses of wine depending on subject's weight. Alcohol will always be consumed in the evening with food or after food (e.g., dinner). The timing of alcohol consumption will be consistent for each individual. Subjects will be provided with red wine for the 2 alcohol intervention weeks. The order of conditions will be random.

"Delayed-eating" / no alcohol

"Delayed-eating" means eating each meal 3 hours later than the "Right-time eating."Subjects will be asked to stick to this eating schedule for 1 week. Subjects will randomly be assigned to each eating pattern during the study period. Subjects will be asked to not drink alcohol for 1 week.

Group Type OTHER

Delayed time eating

Intervention Type OTHER

"Delayed-eating" means eating each meal 3 hours later than the "Right-time eating."Subjects will be asked to stick to this eating schedule for 1 week. Subjects will randomly be assigned to each eating pattern during the study period. Each subject will be required to do this intervention twice during the study period. One time they will have delayed time eating with alcohol , the second time the will have this intervention without alcohol.

Sigmoidoscopy

Intervention Type PROCEDURE

Subjects will undergo unprepped sigmoidoscopy to collect tissue and stool sample at each intervention visits (visit 2, 3, 4, and 5). Flexible sigmoidoscopy will not require any colon cleansing and it will be very limited to the most distal (closest to the end of the anus) 20 centimeters (approximately 8 inches) of the colon and thus will be far less uncomfortable than the routine flexible sigmoidoscopy.

Optional 24h circadian assessment in the Biological Rhythms lab

Intervention Type PROCEDURE

Subjects may choose to participate in the 24 hour circadian assessment in the Biological Rhythms Research Lab. During this assessment, a saliva sample will be taken every hour, a mouth swab will be done every 2 hours, and rectal swab will be done twice (every 12 hours). Subjects will be kept awake in dim light on a recliner chair. Subjects can watch a television with dimmed light. Subjects will be provided with food and drink during the assessment.

If subjects choose this intervention they will be asked to complete 4 assessment during the course of the study period.

"Delayed-eating" / with alcohol

"Delayed-eating" means eating each meal 3 hours later than the "Right-time eating."Subjects will be asked to stick to this eating schedule for 1 week. Subjects will randomly be assigned to each eating pattern during the study period. Moderate alcohol drinking means 0.3-0.5 g/kg alcohol daily, which will be not more than 2 glasses of wine depending on subject's weight. Alcohol will always be consumed in the evening with food or after food (e.g., dinner). The timing of alcohol consumption will be consistent for each individual. Subjects will be provided with red wine for the 1 alcohol intervention week. The order of conditions will be random.

Group Type OTHER

Delayed time eating

Intervention Type OTHER

"Delayed-eating" means eating each meal 3 hours later than the "Right-time eating."Subjects will be asked to stick to this eating schedule for 1 week. Subjects will randomly be assigned to each eating pattern during the study period. Each subject will be required to do this intervention twice during the study period. One time they will have delayed time eating with alcohol , the second time the will have this intervention without alcohol.

Sigmoidoscopy

Intervention Type PROCEDURE

Subjects will undergo unprepped sigmoidoscopy to collect tissue and stool sample at each intervention visits (visit 2, 3, 4, and 5). Flexible sigmoidoscopy will not require any colon cleansing and it will be very limited to the most distal (closest to the end of the anus) 20 centimeters (approximately 8 inches) of the colon and thus will be far less uncomfortable than the routine flexible sigmoidoscopy.

Optional 24h circadian assessment in the Biological Rhythms lab

Intervention Type PROCEDURE

Subjects may choose to participate in the 24 hour circadian assessment in the Biological Rhythms Research Lab. During this assessment, a saliva sample will be taken every hour, a mouth swab will be done every 2 hours, and rectal swab will be done twice (every 12 hours). Subjects will be kept awake in dim light on a recliner chair. Subjects can watch a television with dimmed light. Subjects will be provided with food and drink during the assessment.

If subjects choose this intervention they will be asked to complete 4 assessment during the course of the study period.

Alcohol

Intervention Type OTHER

Moderate alcohol drinking means 0.5 g/kg alcohol daily, which will be not more than 2 glasses of wine depending on subject's weight. Alcohol will always be consumed in the evening with food or after food (e.g., dinner). The timing of alcohol consumption will be consistent for each individual. Subjects will be provided with red wine for the 2 alcohol intervention weeks. The order of conditions will be random.

Interventions

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Right time eating

"Right-time eating" means breakfast before 8am, lunch before 1 pm and dinner before 6pm. Subjects will be asked to stick to this eating schedule for 1 week. Subjects will randomly be assigned to each eating pattern during the study period. Each subject will be required to do this intervention twice during the study period. One time they will have right time eating with alcohol , the second time the will have this intervention without alcohol.

Intervention Type OTHER

Delayed time eating

"Delayed-eating" means eating each meal 3 hours later than the "Right-time eating."Subjects will be asked to stick to this eating schedule for 1 week. Subjects will randomly be assigned to each eating pattern during the study period. Each subject will be required to do this intervention twice during the study period. One time they will have delayed time eating with alcohol , the second time the will have this intervention without alcohol.

Intervention Type OTHER

Sigmoidoscopy

Subjects will undergo unprepped sigmoidoscopy to collect tissue and stool sample at each intervention visits (visit 2, 3, 4, and 5). Flexible sigmoidoscopy will not require any colon cleansing and it will be very limited to the most distal (closest to the end of the anus) 20 centimeters (approximately 8 inches) of the colon and thus will be far less uncomfortable than the routine flexible sigmoidoscopy.

Intervention Type PROCEDURE

Optional 24h circadian assessment in the Biological Rhythms lab

Subjects may choose to participate in the 24 hour circadian assessment in the Biological Rhythms Research Lab. During this assessment, a saliva sample will be taken every hour, a mouth swab will be done every 2 hours, and rectal swab will be done twice (every 12 hours). Subjects will be kept awake in dim light on a recliner chair. Subjects can watch a television with dimmed light. Subjects will be provided with food and drink during the assessment.

If subjects choose this intervention they will be asked to complete 4 assessment during the course of the study period.

Intervention Type PROCEDURE

Alcohol

Moderate alcohol drinking means 0.5 g/kg alcohol daily, which will be not more than 2 glasses of wine depending on subject's weight. Alcohol will always be consumed in the evening with food or after food (e.g., dinner). The timing of alcohol consumption will be consistent for each individual. Subjects will be provided with red wine for the 2 alcohol intervention weeks. The order of conditions will be random.

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

1. Adults (greater than 21 years old)
2. Have had advanced tubular adenoma within the last year

Exclusion Criteria

1. Asian ethnicity (Due to common polymorphisms of enzymes involved in alcohol metabolism)
2. Does not drink alcohol
3. Alcohol use disorder/Alcohol Abuse
4. A known genetic predisposition to colorectal cancer (FAP, Lynch syndrome)
5. A history of colorectal cancer or inflammatory bowel diseases
6. Presence of comorbidities that might affect the circadian system

1. Chronic renal failure
2. Cirrhosis
3. Advanced neurological conditions (e.g., Parkinson's, MS, epilepsy)
4. Psychological disorders (e.g., PTSD, major depression)
5. Sleep apnea
6. Restless Leg Syndrome
7. Inpatient Status
8. Advanced cardiac failure
9. Night shift workers with active shift work in the past month
10. Planned shift work that will occur during the study
11. Crossed more than two time zones in the previous week
7. Conditions that alter or necessitate a particular eating pattern (e.g., uncontrolled diabetes, eating disorders)
8. Conditions that alter the microbiota (infection or recent history of antibiotic use within three months, or use of pro/prebiotics within one month prior to recruitment)
9. Regular use of medications that can potentially affect melatonin profiles (e.g., Melatonin, Metoclopramide, Psychotropic medications, Hypnotics during the four weeks prior to the study)
10. Any active cancer
11. Inability to sign an informed consent
Minimum Eligible Age

21 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Rush University Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Ali Keshavarzian

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Ali Keshavarzian, MD

Role: PRINCIPAL_INVESTIGATOR

Rush University Medical Center

Locations

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Rush University Medical Center

Chicago, Illinois, United States

Site Status

Countries

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United States

Provided Documents

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Document Type: Study Protocol: AFT with cover page

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

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16051904

Identifier Type: -

Identifier Source: org_study_id

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