Sleep and Survival in Colorectal Cancer

Sleep-wake Rhythm in the Perioperative Period in Patients Admitted for Elective Radical Surgery for Colorectal Cancer: an Observational Prospective Cohort Study.

Objective The objective of the current trial is to investigate the effect of perioperative sleep and circadian rhythm on the natural course of survival among patient diagnosed with colorectal cancer. Concurrently, outcome measures like depression, fatigue, quality of life, and co-morbidity will be measured continuously in the short-, intermediate- and long-term period following diagnosis.

The a-priori hypothesis is that preoperative sleep and circadian disturbances is a prognostic marker of reduced overall survival. Likewise, preoperative sleep-wake disturbances at baseline are expected to result in overall universally reduced quality of life, increased depression and fatigue. Furthermore, development of sleep-wake disturbances in the postoperative period as compared to preoperative sleep-wake rhythm is expected to a prognostic marker of negative outcomes.

Target and study population The study population are all patients diagnosed with colorectal cancer in Region Zealand recruited consecutively from the trial initiation until study end each patient with an intended 5 year follow-up period. All available cases will be included in the trial.

Study design The study will be an observational prospective cohort study applying a longituditional repeated measure design.

Exposures and outcomes of interest The primary outcomes in the trial are sleep and circadian outcomes measured via actigraphy in the perioperative period.

Furthermore, cancer related survival and overall survival in the 5 year follow-up period is considered primary outcomes.

Secondary outcomes consist of consecutively measured depression, fatigue, quality of life, follow-up treatment and co-morbidity.

Exposure variables are primary related to the cancer, i.e. cancer stage, surgical treatment, oncological treatment, baseline co-morbidity and pharmacological treatment. Some of the secondary outcomes could be expected to serve as confounding or mediating factors.

Meaningful control for confounding will in the analysis phase be cancer stage and baseline sleep-wake rhythm status.

Sampling methods All available cases will be sought included in the trial. No formal sample size has been performed and continues inclusion into the trial will be performed during an 1,5 year period.

Statistical analyses The relationship between overall survival and baseline sleep-wake rhythm will be investigated using survival statistics and/or multivariate logistic regression.

Expected results The investigators expect to see a marked difference in overall survival among patients with sleep and circadian disturbances at baseline.

Study Overview

• Status: Active, not recruiting
• Conditions: Depression; Quality of Life; Sleep; Colorectal Neoplasm; Circadian Rhythm Sleep Disorder
• Intervention / Treatment: Other: Standard of care

• Study Type: Observational
• Enrollment (Actual): 45

Contacts and Locations

Study Locations

• Denmark
  • Zealand
    • Roskilde, Zealand, Denmark, 4000
      • Department of Surgery, Zealand University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

All patients eligible for elective curative intended surgery for colonic or rectal adenocarcinoma at Zealand University Hospital.

Description

Inclusion Criteria:

• Diagnosis of colorectal cancer as determined at the multi-disciplinary team conference.
• Admitted to elective radical surgery at the department of surgery at Zealand University Hospital
• Age above 18 years
• Informed consent

Exclusion Criteria:

• Non-ability to complete the study as assessed by the investigator
• Non-fluent in Danish.
• History of cognitive impairment (e.g. dementia)
• Paralysis or inability to answer study questioners electronically.
• Stadium 4 colonic adenocarcinoma with no surgical treatment options as determined at the multi-disciplinary conference.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Colorectal cancer undergoing elective surgery; All patients eligible for elective curative intended surgery for colonic adenocarcinoma at Zealand University Hospital. Patients will recieve treatment as per standard of care.	Other: Standard of care; Elective radical surgery for adenocarcinoma.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Actigraphy	Assessment of activity using accelerometor - Sleep and circadian assesment.	Approximately 1 week preoperatively to 2 weeks postoperatively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major Depression Inventory	Assesment of depression	Baseline (approx. 1 week preoperatively), 2 weeks postoperatively, 3 months postoperatively, 6 months postoperatively, 12 months postoperativly, 24 months postoperatively, 36 months postoperatively, 60 months postoperatively.
Insomnia Severity Index	Subjective sleep assesment	Baseline (approx. 1 week preoperatively), 2 weeks postoperatively, 3 months postoperatively, 6 months postoperatively, 12 months postoperativly, 24 months postoperatively, 36 months postoperatively, 60 months postoperatively.
Quality of life assesment	EORCT-QLQ-C30	Baseline (approx. 1 week preoperatively), 2 weeks postoperatively, 3 months postoperatively, 6 months postoperatively, 12 months postoperativly, 24 months postoperatively, 36 months postoperatively, 60 months postoperatively.
Quality of life assesment	EORCT-QLQ-CR29	Baseline (approx. 1 week preoperatively), 2 weeks postoperatively, 3 months postoperatively, 6 months postoperatively, 12 months postoperativly, 24 months postoperatively, 36 months postoperatively, 60 months postoperatively.
Mortality	Baseline registration and follow-up assessments	Baseline (approx. 1 week preoperatively), 2 weeks postoperatively, 3 months postoperatively, 6 months postoperatively, 12 months postoperativly, 24 months postoperatively, 36 months postoperatively, 60 months postoperatively.
Co-morbidity	Baseline registration and follow-up assessments	Baseline (approx. 1 week preoperatively), 2 weeks postoperatively, 3 months postoperatively, 6 months postoperatively, 12 months postoperativly, 24 months postoperatively, 36 months postoperatively, 60 months postoperatively.
Drug prescription history (Drug name and dosage)	Baseline registration and follow-up assessments	Baseline (approx. 1 week preoperatively), 2 weeks postoperatively, 3 months postoperatively, 6 months postoperatively, 12 months postoperativly, 24 months postoperatively, 36 months postoperatively, 60 months postoperatively.
Follow-up cancer treatment (Adjuvant chemotherapy, timing and duration)	Baseline registration and follow-up assessments	Baseline (approx. 1 week preoperatively), 2 weeks postoperatively, 3 months postoperatively, 6 months postoperatively, 12 months postoperativly, 24 months postoperatively, 36 months postoperatively, 60 months postoperatively.

Collaborators and Investigators

• Sponsor: Zealand University Hospital
• Collaborators: Center of Surgical Science, Department of Surgery, Zealand University Hospital
• Investigators: Principal Investigator: Michael T Madsen, M.D., Department of Surgery, Zealand University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2017
• Primary Completion (Actual): July 31, 2018
• Study Completion (Anticipated): July 31, 2023

Study Registration Dates

• First Submitted: August 15, 2017
• First Submitted That Met QC Criteria: August 18, 2017
• First Posted (Actual): August 21, 2017

Study Record Updates

• Last Update Posted (Actual): January 15, 2019
• Last Update Submitted That Met QC Criteria: January 13, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: Actigraphy; Insomnia Severity Index (ISI); Major Depression Inventory (MDI)
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Digestive System Diseases; Nervous System Diseases; Neoplasms; Dyssomnias; Neoplasms by Site; Neurologic Manifestations; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Occupational Diseases; Intestinal Neoplasms; Rectal Diseases; Chronobiology Disorders; Depression; Sleep Wake Disorders; Colorectal Neoplasms; Sleep Disorders, Circadian Rhythm
• Other Study ID Numbers: MTM-V3; SJ-600 (Other Identifier: Region Zealand ethics Comittee)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Contact to study investigators avaliable at mitm@regionsjaelland.dk

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No