Back to resultsThe Effect of Melatonin in Patients With Low Anterior Resection Syndrome (MELLARS)
Primary Purpose
Low Anterior Resection Syndrome
Status
Active
Phase
Phase 2
Locations
Denmark
Study Type
Interventional
Intervention
Melatonin
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Low Anterior Resection Syndrome
Eligibility Criteria
Inclusion Criteria:
- Patients should have major LARS (LARS score >29).
- Patients should have undergone bowel continuity restoring surgery between the last 3 to 24 months.
- Participants should be 18 years or older.
- Participants must sign an informed consent form.
Exclusion Criteria:
- Known allergic reaction to melatonin.
- Dementia as determined by mini mental state examination score (MMSE) < 24.
- Participation in another pharmacological intervention trial at the point of inclusion.
- Completed any adjuvant oncological treatment within the last three months.
- Ongoing oncological treatment.
- Rotor or Dubin-Johnson syndrome, epilepsy, systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Parkinson's disease, spinal cord injury and multiple sclerosis.
- Severe liver disease defined as transaminases above 3 times the normal levels, and severe kidney disease defined as eGFR below 40 ml/min.
- Daily ongoing hypnotic treatment.
- Pre-existing medical sleep disorder diagnosed before the diagnosis of rectal cancer (i.e sleep apnea, restless legs, narcolepsy.)
- Work involving nightshifts.
- Daily alcohol consumption above 5 units of alcohol (1 unit = 12 g alcohol)
- Predictable poor compliance (due to pre-existing psychiatric disease, dementia or not able to read or speak sufficient Danish)
- Pregnant or breastfeeding.
- Severe, life-threatening medical condition, that implies that the patient cannot participate in the study course. (e.g. metastatic disease, local recurrence, stroke, AMI).
- Females not in menopause (defined as no menstruation during the last 12 months) should not be pregnant. Furthermore, reproductive females should use a secure birth control (intrauterine devices, hormonal contraceptives including - oral pills, patches, vaginal rings and injections) during the entire period of the trial.
Sites / Locations
- Zealand University Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Melatonin-Placebo sequence
Placebo-Melatonin sequence
Arm Description
50% of the included patients will receive 4 weeks of treatment with melatonin, followed by a 4 week wash out period, and then 4 weeks of treatment with placebo. The treatments are blinded.
50% of the included patients will receive 4 weeks of treatment with placebo, followed by a 4 week wash out period, and then 4 weeks of treatment with melatonin. The treatments are blinded.
Outcomes
Primary Outcome Measures
Change in Low Anterior Resection Syndrome Score
The LARS Score questionnaire is filled out by the participants before and after each treatment period.
Secondary Outcome Measures
Daily bowel function
The participants will fill out a diary on the daily bowel movements during the treatment phase
Self-reported quality of life
EORTC Quality of Life Questionnaire for cancer patients and specifically colorectal cancer patients
Other patient reported symptoms
Measure Yourself Medical Outcome Profile (MYMOP) is a self-administered questionnaire. Patients are asked to specify one or two symptoms that concern them the most. Subsequently they evaluate the severity on a 7-point Likert scale. The second part of the questionnaire uses the same scale to assess whether the symptom limits or prevent any daily activity, and also to rate general well-being. Follow-up questionnaires address the original issues completed in the initial form. Symptom 1, symptom 2, activity, and wellbeing each have a separate score between 0 and 6 with 0 indicating "as good as it could be" and 6 "as bad as it could be". An overall score is calculated by taking the average of item scores.
Anxiety
Hospital Anxiety and Depression Scale (HADS-A): The anxiety subscale consists of 7 questions which are graded on a 4 point scale (0-1-2-3) and is summed into a total score between 0-21. A score of 7 or lower is negative case, a score of 8 - 10 is a doubtful case, and a score of 11 or above is a positive case.
Depression
Hospital Anxiety and Depression Scale (HADS-D): The depression subscale consists of 7 questions which are graded on a 4 point scale (0-1-2-3) and is summed into a total score between 0-21. A score of 7 or lower is negative case, a score of 8 - 10 is a doubtful case, and a score of 11 or above is a positive case.
Sleep
Participants will wear an actigraph during the treatment phases and fill out a sleep diary and this will allow to asses sleep time (minutes).
Insomnia
Insomnia Severity Index (ISI)
Incidence of treatment-emergent Adverse Effects [Safety and reactions]
Participants will be systematically interviewed before and after the treatment periods.
Melatonin
Blood samples will be taken after each treatment ends.
Multiplex gene assay - NanoString nCounter® Inflammation Panel analysis in blood
Difference in gene expressions between intervention and placebo groups
Motilin
Blood samples will be taken after each treatment ends.
Pathological assessment of inflammation
Rectal biopsies will be taken after each treatment ends.The FFPE treated biopsies will be assessed by pathologist using a routine inflammatory grading system to asses inflammation
Multiplex gene assay - NanoString nCounter® Inflammation Panel analysis in biopsies
Difference in gene expressions between intervention and placebo groups
Motilin receptors
Rectal biopsies will be taken after each treatment ends.
Full Information
NCT ID
NCT05042700
First Posted
August 30, 2021
Last Updated
April 24, 2023
Sponsor
Ismail Gögenur
Collaborators
Hvidovre University Hospital, Aarhus University Hospital
1. Study Identification
Unique Protocol Identification Number
NCT05042700
Brief Title
The Effect of Melatonin in Patients With Low Anterior Resection Syndrome
Acronym
MELLARS
Official Title
The Effect of Melatonin in Patients With Low Anterior Resection Syndrome
Study Type
Interventional
2. Study Status
Record Verification Date
April 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
October 13, 2021 (Actual)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
December 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Ismail Gögenur
Collaborators
Hvidovre University Hospital, Aarhus University Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The primary objective of the study is to investigate whether treatment with melatonin has an alleviating effect on Low Anterior Resection Syndrome (LARS) symptoms. Secondarily, the effect of the treatment on bowel movements, other patient reported symptoms, quality of life, depression, anxiety, sleep disturbances, motilin levels, and microscopic changes in rectal mucosa will be investigated.
Detailed Description
This trial which will be conducted in two phases.
The first part of the study will be conducted as an internal feasibility test. Three patients with major LARS will be included. Patients will be recruited from the Department of Surgery, Zealand University Hospital. These patients will not be randomized nor blinded. They will receive a 4-week treatment with 25 mg melatonin and will undergo the same questionnaires and tests before and after treatment as in the randomized clinical trial. The preliminary results from the internal feasibility test will allow us to assess potential difficulties related to the administration or design, which then will be able to be corrected before the randomization part is initiated.
The second part of the will be conducted as a randomized, blinded, placebo-controlled, crossover study and will be testing whether treatment with melatonin has an alleviating effect on Low Anterior Resection Syndrome (LARS) symptoms.
Patients will be randomized to receive 4 weeks of treatment with melatonin, followed by a 4 week wash out period, and then 4 weeks of treatment with placebo (M-P) or 4 weeks of treatment with placebo, followed by a 4 week wash out period, and then 4 weeks of treatment with melatonin (P-M). Both participants and investigators will be blinded.
Patients will be given questionnaires before and after each treatment period to assess outcomes. Blood samples and rectal biopsies will be taken after each treatment period.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Low Anterior Resection Syndrome
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
21 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Melatonin-Placebo sequence
Arm Type
Experimental
Arm Description
50% of the included patients will receive 4 weeks of treatment with melatonin, followed by a 4 week wash out period, and then 4 weeks of treatment with placebo. The treatments are blinded.
Arm Title
Placebo-Melatonin sequence
Arm Type
Experimental
Arm Description
50% of the included patients will receive 4 weeks of treatment with placebo, followed by a 4 week wash out period, and then 4 weeks of treatment with melatonin. The treatments are blinded.
Intervention Type
Drug
Intervention Name(s)
Melatonin
Intervention Description
Enema with 25 mg melatonin
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Enema without melatonin
Primary Outcome Measure Information:
Title
Change in Low Anterior Resection Syndrome Score
Description
The LARS Score questionnaire is filled out by the participants before and after each treatment period.
Time Frame
4 weeks
Secondary Outcome Measure Information:
Title
Daily bowel function
Description
The participants will fill out a diary on the daily bowel movements during the treatment phase
Time Frame
4 weeks
Title
Self-reported quality of life
Description
EORTC Quality of Life Questionnaire for cancer patients and specifically colorectal cancer patients
Time Frame
4 weeks
Title
Other patient reported symptoms
Description
Measure Yourself Medical Outcome Profile (MYMOP) is a self-administered questionnaire. Patients are asked to specify one or two symptoms that concern them the most. Subsequently they evaluate the severity on a 7-point Likert scale. The second part of the questionnaire uses the same scale to assess whether the symptom limits or prevent any daily activity, and also to rate general well-being. Follow-up questionnaires address the original issues completed in the initial form. Symptom 1, symptom 2, activity, and wellbeing each have a separate score between 0 and 6 with 0 indicating "as good as it could be" and 6 "as bad as it could be". An overall score is calculated by taking the average of item scores.
Time Frame
4 weeks
Title
Anxiety
Description
Hospital Anxiety and Depression Scale (HADS-A): The anxiety subscale consists of 7 questions which are graded on a 4 point scale (0-1-2-3) and is summed into a total score between 0-21. A score of 7 or lower is negative case, a score of 8 - 10 is a doubtful case, and a score of 11 or above is a positive case.
Time Frame
4 weeks
Title
Depression
Description
Hospital Anxiety and Depression Scale (HADS-D): The depression subscale consists of 7 questions which are graded on a 4 point scale (0-1-2-3) and is summed into a total score between 0-21. A score of 7 or lower is negative case, a score of 8 - 10 is a doubtful case, and a score of 11 or above is a positive case.
Time Frame
4 weeks
Title
Sleep
Description
Participants will wear an actigraph during the treatment phases and fill out a sleep diary and this will allow to asses sleep time (minutes).
Time Frame
4 weeks
Title
Insomnia
Description
Insomnia Severity Index (ISI)
Time Frame
4 weeks
Title
Incidence of treatment-emergent Adverse Effects [Safety and reactions]
Description
Participants will be systematically interviewed before and after the treatment periods.
Time Frame
4 weeks
Title
Melatonin
Description
Blood samples will be taken after each treatment ends.
Time Frame
4 weeks
Title
Multiplex gene assay - NanoString nCounter® Inflammation Panel analysis in blood
Description
Difference in gene expressions between intervention and placebo groups
Time Frame
4 weeks
Title
Motilin
Description
Blood samples will be taken after each treatment ends.
Time Frame
4 weeks
Title
Pathological assessment of inflammation
Description
Rectal biopsies will be taken after each treatment ends.The FFPE treated biopsies will be assessed by pathologist using a routine inflammatory grading system to asses inflammation
Time Frame
4 weeks
Title
Multiplex gene assay - NanoString nCounter® Inflammation Panel analysis in biopsies
Description
Difference in gene expressions between intervention and placebo groups
Time Frame
4 weeks
Title
Motilin receptors
Description
Rectal biopsies will be taken after each treatment ends.
Time Frame
4 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients should have major LARS (LARS score >29).
Patients should have undergone bowel continuity restoring surgery between the last 3 to 24 months.
Participants should be 18 years or older.
Participants must sign an informed consent form.
Exclusion Criteria:
Known allergic reaction to melatonin.
Dementia as determined by mini mental state examination score (MMSE) < 24.
Participation in another pharmacological intervention trial at the point of inclusion.
Completed any adjuvant oncological treatment within the last three months.
Ongoing oncological treatment.
Rotor or Dubin-Johnson syndrome, epilepsy, systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Parkinson's disease, spinal cord injury and multiple sclerosis.
Severe liver disease defined as transaminases above 3 times the normal levels, and severe kidney disease defined as eGFR below 40 ml/min.
Daily ongoing hypnotic treatment.
Pre-existing medical sleep disorder diagnosed before the diagnosis of rectal cancer (i.e sleep apnea, restless legs, narcolepsy.)
Work involving nightshifts.
Daily alcohol consumption above 5 units of alcohol (1 unit = 12 g alcohol)
Predictable poor compliance (due to pre-existing psychiatric disease, dementia or not able to read or speak sufficient Danish)
Pregnant or breastfeeding.
Severe, life-threatening medical condition, that implies that the patient cannot participate in the study course. (e.g. metastatic disease, local recurrence, stroke, AMI).
Females not in menopause (defined as no menstruation during the last 12 months) should not be pregnant. Furthermore, reproductive females should use a secure birth control (intrauterine devices, hormonal contraceptives including - oral pills, patches, vaginal rings and injections) during the entire period of the trial.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ismail Gögenur, DMSc
Organizational Affiliation
Zealand University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Zealand University Hospital
City
Køge
State/Province
Region Sjælland
ZIP/Postal Code
4600
Country
Denmark
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
The Effect of Melatonin in Patients With Low Anterior Resection Syndrome
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