The Dept. of Medicine, National University Hospital is conducting a clinical study on using low dose melatonin to treat patients with irritable bowel syndrome (IBS) with sleep disturbance. This study has been approved by the Institutional Review Board. For this study, we are looking for volunteers.
We will provide free examination and diagnosis for people (males & females 20-68 years old) who have bowel symptoms (abdominal pain with bloating/diarrhea/constipation) and sleep disturbance to see if you have irritable bowel syndromes (IBS). If you are confirmed to have IBS, you will be asked to take part in this study. The suitable subject will be reimbursed S$400 for the time spent in the study.
For more information, please contact us at Mon- Sat from 9.00 am-5.00 pm
Tel: Miss Shelia: 67724084 or 92568272(pager)
Dr. Song 67795555 Extension 2366
E-mail: g0203394@nus.edu.sg
Details of the study is described below ( 详细试验细节如下)
Double blind randomised placebo controlled trial of low dose melatonin for sleep disorders in irritable bowel syndrome
Subject Information sheet
Irritable bowel syndrome (IBS) is common in the community. The cause of IBS is not exactly clear. Sleep disturbance is commonly observed in patients with IBS. Conversely, poor sleep has also been shown to lead to more frequent gastrointestinal symptoms among women with IBS. One study showed that patients with IBS pain have a lower urinary excretion of 6-sulphatoxy melatonin, a metabolite of melatonin and a circadian rhythm of lower amplitude. The result suggests that abnormal secretion of melatonin may be involved in the onset of sleep disturbance in IBS patients.
Melatonin is a hormone secreted by the pineal gland. It has been implicated in the control of the sleep-wake cycle. Its secretion is stimulated during darkness and suppressed by light. At present, melatonin is extensively used as a self-administered remedy for sleep disturbance and jetlag in Singapore where it is freely available. Although the pineal gland is the primary source of melatonin, the hormone is also detected in high concentrations in the gastrointestinal tract.
Indeed, we showed in a previous trial that oral melatonin improved IBS symptoms. We therefore concluded that melatonin was a promising agent for treating IBS. However, the study had only a small number of subjects. Further investigations are needed to confirm the efficacy of melatonin in treating IBS. Based on the above finding and the fact that IBS may be related to sleep disturbance, we propose that the therapeutic effects of melatonin may be most evident if this medication is used in IBS patients who suffer from sleep disturbance as well.
1. What are the purposes of the study?
We would like to seek your permission to enroll you in this study. The purpose of the study is to investigate the effectiveness of low-dose slow-release melatonin in treating sleep disturbance and symptoms of IBS in IBS patients. Finally, we will like to know if the melatonin’s effect on IBS is related to its action on sleep disturbances.
2. What do the subjects need to do?
If you agree to participate in the study, you will be required to answer a series of questionnaires to determine your symptoms. You will then be asked to undergo the following tests:
1. Rectal sensitivity study (Barostat test；直肠敏感性试验): One thin flexible balloon tube will be inserted into your rectum. The balloon is inflated with progressively increasing volumes of air until the discomfort threshold is reached or to a maximal volume of 120ml. From this study, we will measure the lowest balloon volumes required to induce sensations of wind, desire to defaecate, urgency of defecation and discomfort.
2. EEG(electroencephalography; 脑电图): You will be asked to undergo an overnight study at your home. Our technician will go to your home to install EEG machine, at which time electrodes will be applied to monitor brain waves and eye movements to see if you are asleep. In the next morning, our technician will come again to collect the data and take apart the machine.
3. Measurement of saliva melatonin and urine 6-sulphatoxy melatonin.
During the EEG night, you will be asked to offer 2 ml saliva at 9-11 PM, and in the next morning 2 ml saliva and 10 ml urine will also be collected.
You will then be randomly assigned to taking melatonin, one tablet at night, or a placebo tablet at a similar dose, for 2 weeks. Your chance of being assigned to either melatonin or the placebo tablet is about equal and you will not be able to choose which one. Neither you nor your doctor will know which tablets you will be taking. The frequency and severity of bowel symptoms and sleep pattern will be recorded on a diary at the start of the study, and daily for two weeks while you are taking the tablets.
At the end of the second week, you will be asked to return to the clinic for review. The series of tests, which are done before melatonin treatment, will be repeated to assess for any changes. The study will finish at that time.
3. Will I be paid for participating in this study?
You will be given a token ($400) to compensate for time loss, trouble incurred and travel expenses at the end of this study.
4. Where will the study take place?
You will be seen in the National University Hospital for your assessment. Rectal sensitivity study will be carried out at the Endoscopy Centre
5. Who can participate?
You have been selected because you are a IBS patient with sleep disturbance. We hope to recruit a total of 50 male or female subjects.
To participate in the study, the following must be satisfied:
You should be aged 18-68 years old, male or female IBS patients with sleep disturbance.
To participate in the study, the following must be absent to all participants:
1. Pregnant or breast-feeding females.
2. Those have organic gastrointestinal, anal, hepatic or other systemic disorders.
3. Previous gastrointestinal surgery except gallbladder surgery and appendectomy.
4. History of cerebral disease.
5. Ongoing treatment with any drug that will influence this study, treatment with any investigational drug during the preceding 30 days, pregnancy or lactation.
6. Are there any risks or discomfort involved?
Barostat test is a very safe procedure which has been carried out in many countries such as USA and UK. Moreover, the research nurse who will be doing the rectal sensitivity test is very experienced. Upon balloon distension, you may experience sensations of fell, desire to defaecate, urgency of defecation and pain/discomfort. However, the balloon will be deflated as soon as significant pain/discomfort is reported. The computerised inflation pump system ensures that the volumes of air can be delivered with a high degree of accuracy.
EEG is a very safe produce and is not known to induce any obvious side-effects.
Melatonin is a well-established medication that has been used to treat sleep disturbance. It has an extremely safe track record. So far, no serious adverse effects have been reported.
If you follow the directions of the doctors in charge of this study and you are adversely affected or physically injured due to the trial substance or procedure properly given under the plan for this study, the NUH will pay the medical expenses for the treatment of that adverse event/injury. Payment for management of the normally expected consequences of your treatment will not be provided by NUH. There will be no guarantee of efficacy for the treatment.
7. What are the advantages of the study?
The study will help us have a better understand the aetiology, pathophysiology of IBS and the sleep disturbance of IBS.
8. Possible benefits for you
If you are a patient with this condition, this study may help to determine the cause of your symptom. This may enable us to tailor your treatment accordingly. The study may also help us to determine if the medication is effective to treat your symptoms. You will get free medical care from our specialist consultants, and free medication (melatonin).
9. Confidentiality and disclosure
Anything you say will be treated in confidence. Data obtained from the study will be stored in a safe place and will be treated in confidence. They will only be used for this particular study. Your records will not be made publicly available. If the results of the study are published, your identity will remain strictly confidential.
10. Is there any cost incurred?
You will not be charged for the various tests. If you are currently hospitalised, participation in this study should not lengthen your stay.
11. Do I have to participate in this study?
No, you don’t. The participation is voluntary. If you disagree, we will be unable to enrol you into our study. You may also withdraw from the study, at any time, without penalty or loss of benefits to which you are otherwise entitled. At any point of the study, if you are found to be pregnant or lactating, the investigator will terminate your participation without regard to your consent.
12. Who do I contact for questions?
If you have any question regarding the study, or you would like more information about the study, please contact Ms Shelia at telephone number 67724084 or pager number 92568272. or Dr. Song Guanghui at tell 67795555 extention 2366.
Email: g0203394@nus.edu.sg
