Circadian Disturbances After Breast Cancer Surgery

Study Overview
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Brief Summary
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The purpose of this study is to investigate circadian disturbances after breast cancer surgery by means of monitoring sleep and heart-rate variability, by measuring a metabolite of melatonin in urine and by questionnaires and a sleep-diary.

Detailed Description
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An increasing number of studies have shown that circadian variation in the excretion of hormones, the sleep-wake cycle, the core body temperature, the tone of the autonomic nervous system and the activity rhythm are important both in health and disease processes. More attention is being paid towards the circadian variation in endogenous rhythms in relation to surgery and whether this can affect postoperative recovery, morbidity and mortality. Studies have been done on circadian disturbances after major and minor surgery but never in relation to breast cancer surgery. This study will investigate circadian disturbances in this specific group of patients by using Actigraphy, Polysomnography (PSG), Holter-monitoring (HRV), the primary metabolite of melatonin in urine 6-sulfatoxymelatonin (aMT6s), questionnaires and a sleep-diary.

Official Title
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Circadian Disturbances After Breast Cancer Surgery

Conditions
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Circadian Rhythm Disorders, Anxiety, Breast Cancer

Intervention / Treatment
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* Device: Wrist-Actigraph - Octagonal Basic Motionlogger, Ambulatory monitoring Inc, New York, USA
* Device: Polysomnograph - Embla A10 (Medcare, Reykjavik, Iceland)
* Device: Holter monitor - Medilog AR12 (Oxford Instruments, Oxford, England)
* Procedure: Urine 6-sulphatoxymelatonin (aMT6s)
* Other: Karolinska Sleepiness Scale
* Other: Visual Analog Scale and 10 point-scales to measure fatigue, general well-being, subjective sleep and pain
* Other: Sleep-diary


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: women, age 30-70, with breast cancer who are admitted for a lumpectomy at Herlev Hospital ASA score I-III Exclusion Criteria: Known sleep apnea Pre-operative treatment with beta-blockers Diabetes Mellitus Known pre-operative depressive illness or dementia Previous or current cancer Known medically treated sleep-disorder (insomnia, restless legs etc) Shift-work Daily alcohol intake of more than 5 units Pre-operative treatment with psychopharmacological drugs, opioids or anxiolytics (including all sleeping pills) Predicted bad compliance Pregnant or breast-feeding Pre- or post-operative complications or events which are expected to increase morbidity or pain the first post-operative days. Missing written consent Pre-operative MMSE score less than 24 Urine or fecal incontinence

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Breast cancer patients<br>12 breast cancer patients aged 30-70 years undergoing a lumpectomy at Herlev Hospital. ASA score I-III. | Device: Wrist-Actigraph - Octagonal Basic Motionlogger, Ambulatory monitoring Inc, New York, USA<br>* Wrist-Actigraph to be worn on the non-dominant arm on day 0-3-17 of the study.<br>Device: Polysomnograph - Embla A10 (Medcare, Reykjavik, Iceland)<br>* Polysomnography on day 0-3-17 of the study. This is a portable polysomnograph with 16 digital channels for recording of electroencephalogram (EEG), electrooculograph (EOG) and electromyograph (EMG).<br>Device: Holter monitor - Medilog AR12 (Oxford Instruments, Oxford, England)<br>* Holter monitoring on day 0-3-17 of the study. Measurements are done by superficial skin-electrodes placed after standardised rules from the producer of the device.<br>Procedure: Urine 6-sulphatoxymelatonin (aMT6s)<br>* Urine sampling for measurement of the primary metabolite of melatonin - 6-sulphatoxymelatonin (aMT6s) will be done on day 0-3-17 of the study. The analysis will be done by a radioimmunoassay.<br>Other: Karolinska Sleepiness Scale<br>* Karolinska Sleepiness Scale to measure sleepiness will be filled out twice a day every day of the entire study period of 17 days.<br>Other: Visual Analog Scale and 10 point-scales to measure fatigue, general well-being, subjective sleep and pain<br>* Visual Analog Scale and 10 point-scales to measure fatigue, general well-being, subjective sleep and pain will be filled out twice a day everyday of the study period of 17 days.<br>Other: Sleep-diary<br>* Sleep-diary to measure subjective sleep quantity will be completed every morning and after every nap in the day.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Preoperative sleep architecture of breast cancer patients | Sleep architecture measured by Polysomnography (awake, stadium I-IV, REM sleep, sleep latency, awakenings). | 1 day preoperatively | 
| Postoperative sleep architecture of breast cancer patients (early phase) | Sleep architecture measured by Polysomnography (awake, stadium I-IV, REM sleep, sleep latency, awakenings) | The first postoperative night | 
| Postoperative sleep architecture of breast cancer patients (late phase) | Sleep architecture measured by Polysomnography (awake, stadium I-IV, REM sleep, sleep latency, awakenings) | The 14th postoperative night | 
| Sleep quality, fatigue, well-being and pain. | Fatigue, generel well-being, subjective sleep and pain scores on a Visual Analog Scale - questionnaires filled out daily. Sleepiness measured by Karolinska Sleepiness Scale. A sleep-diary recording sleep quantity of day and night sleep. | 1 day preoperatively till 14 days postoperatively | 
| Preoperative melatonin levels and amplitude | Excretion of aMT6s in urine. Urine will be collected from 23-07, quantified and 2 samples will be taken to measure aMT6s. | 1 day preoperatively | 
| Postoperative melatonin levels and amplitude (early phase) | Excretion of aMT6s in urine. Urine will be collected from 23-07, quantified and 2 samples will be taken to measure aMT6s. | The first postoperative night | 
| Postoperative melatonin levels and amplitude | Excretion of aMT6s in urine. Urine will be collected from 23-07, quantified and 2 samples will be taken to measure aMT6s. | The 14th postoperative night | 
| Sleep architecture | Actigraphy (total minutes asleep, sleep effectiveness, sleep latency, awakenings). A wrist actigraph wil be worn from 1 day preoperatively and taken off on the 14th postoperative day. | 1 day preoperatively till 14 days postoperatively | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Preoperative heart-rate variability of breast cancer patients | Heart-rate variability measured by Holter monitor and a following analysis of frequency domain parameters. | 1 day preoperatively | 
| Postoperative heart-rate variability of breast cancer patients (early phase) | Heart-rate variability measured by Holter monitor and a following analysis of frequency domain parameters. | The first postoperative night | 
| Postoperative heart-rate variability of breast cancer patients (late phase) | Heart-rate variability measured by Holter monitor and a following analysis of frequency domain parameters. | The 14th postoperative night | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Circadian Rhythm Disorders, Breast Neoplasms Surgery, Sleep, Heart Rate