Frequency of Sleep Abnormalities in Patients With Irritable Bowel Syndrome and Effect of Pharmacological Intervention

NCT ID: NCT04193501

Last Updated: 2020-03-16

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 194 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-02-01
• Study Completion Date: 2022-02-28

Brief Summary

Irritable bowel syndrome (IBS), a common gastrointestinal (GI) disorder in India and in the rest of the World, is enigmatic in its pathogenesis. IBS is associated with recurrent abdominal pain or discomfort, bloating, incomplete evacuation, altered bowel habits, and abnormal stool forms. The etiology of IBS remains unclear and different factors were thought to be involved like genetics and environmental factors, visceral hypersensitivity, altered gut microbiota or disorder of the microbiota-gut-brain axis and various psychological factors like anxiety, depression, and insomnia or sleep disturbance. Due to increasing work pressure in today's society, and the consequent shift duty and psychological stress, the frequency of sleep disorders is increasing; disturbed sleep may be associated with a vicious cycle in which altered sleep may result in gastrointestinal (GI) disturbances, which in turn, may jeopardize sleep further. The disorder of the gut microbiota, the largest organ of the human body, is being suggested to be responsible for several GI and extra-GI diseases. Qualitative change in gut microbiota is currently studied by next-generation sequencing. Gut and sleep patterns work in an axis - a two-way street of communication, some studies reported altered gut microbiota or dysbiosis modulates peripheral and central nervous system function, leading to alterations in brain signaling and behavior that possibly leads to sleep disturbances.

Detailed Description

Irritable bowel syndrome (IBS), a common gastrointestinal (GI) disorder in India and in the rest of the World, is enigmatic in its pathogenesis. IBS is associated with recurrent abdominal pain or discomfort, bloating, incomplete evacuation, altered bowel habits, and abnormal stool forms. The etiology of IBS remains unclear and different factors were thought to be involved like genetics and environmental factors, visceral hypersensitivity, altered gut microbiota or disorder of the microbiota-gut-brain axis and various psychological factors like anxiety, depression, and insomnia or sleep disturbance. Due to increasing work pressure in today's society, and the consequent shift duty and psychological stress, the frequency of sleep disorders is increasing; disturbed sleep may be associated with a vicious cycle in which altered sleep may result in gastrointestinal (GI) disturbances, which in turn, may jeopardize sleep further. The disorder of the gut microbiota, the largest organ of the human body, is being suggested to be responsible for several GI and extra-GI diseases. Qualitative change in gut microbiota is currently studied by next-generation sequencing. Gut and sleep patterns work in an axis - a two-way street of communication, some studies reported altered gut microbiota or dysbiosis modulates peripheral and central nervous system function, leading to alterations in brain signaling and behavior that possibly leads to sleep disturbances.

Several case-control and meta-analyses have reported an association between sleep disturbance and irritable bowel syndrome (IBS) as compared to healthy controls. However, the data regarding the relationship between sleep disturbance and severity parameters of IBS have not been widely reported; moreover, interventions that improve disturbed sleep on these parameters are scanty. There is no systematic study on sleep disorders among patients with IBS from India.

Melatonin is a hormone made by the pineal gland; its biosynthesis is initiated by the uptake of the essential amino acid tryptophan and is an important inducer of sleep. Abnormality in melatonin has been shown in several studies on patients of IBS and functional constipation. A few studies also reported improvement in sleep and GI function after the administration of melatonin. However, these studies had limitations due to the small sample size, lack of randomization and inclusion of patients without the sleep disorder. Moreover, there is no study from India on this issue.

Accordingly, investigators wish to undertake a study with the following aims: (i) Quality of sleep among patients with IBS and healthy controls. (ii) Levels of 6-Hydroxymelatonin sulphate (a metabolite of melatonin) both in patients with IBS and healthy controls.

(iii) Relationship between the IBS symptom severity (IBS-SSS), Health-Related Quality of Life (HRQL) and sleep disorder and melatonin deficiency, (iv) Relationship between sleep quality and rectal sensory function (by barostat) (v) Relationship between gut dysbiosis and the IBS symptom severity (IBS-SSS), Health-Related Quality of Life (HRQL) and sleep disorder (vi) Effect of melatonin administration on IBS symptoms, HRQL, and sleep. Since sleep disturbance may be an important issue in IBS, the patients with IBS will be treated both with melatonin and standard treatment. Parameters like IBS-SSS, HRQL, Hospital Anxiety and Depression Scale (HADS) score, Pittsburgh Sleep Quality Index (PSQI) will be studied in patients with IBS and healthy controls and these parameters would be repeated after 1 and 3 months follow-up in patients only. Urinary 6-Hydroxymelatonin sulphate will be studied in patients and controls before treatment with standard medical therapy (SMT) plus melatonin and it will be repeated after one month among patients with IBS only. The sleep study will be performed by the PSQI questionnaire and also by polysomnography depending on the availability of the instrument. The rectal sensory function will be studied by barostat. The study will analyse the effect of melatonin in GI and sleep disorder functions. Data will be analyzed using appropriate statistical techniques. P-values lesser than 0.05 will be considered significant.

Study protocol:

Sample size:

The related case-control studies were reviewed for the calculation of sample size. The frequency of sleep disorder among IBS was observed to be 35% and 43% whereas in control it has been observed to be 29 and 14% respectively. Taking the average of these, investigators considered among IBS case and controls the average frequency of sleep disorder is 40% and 22%, respectively, considering a power of 80%, alpha value of 0.05 and ratio of the case to control is 1:1. As per the calculation, investigators propose to include 97 cases and 97 controls.

For an interventional study with SMT plus melatonin and SMT plus placebo, the sample size was calculated based on the data that improvement occurred in 88% patients if treated with SMT plus melatonin as compared to 47% with SMT plus placebo. Hence, 34 patients will be treated with SMT plus melatonin and 34 with SMT plus placebo (two-sided CI 99%, power 80%, case: control 1:1, and p-value <0.05). Considering 20-25% loss to follow-up, 97 patients with IBS will be randomized to SMT plus melatonin and SMT plus placebo.

Actual plan of work:

Study site:

This study will be conducted in the Department of Gastroenterology, in inter-departmental collaborations with the Department of Neurology to analyse the effect of SMT plus melatonin in GI and sleep.

Inclusion criteria

• Diagnosis by ROME III/IV criteria.
• Willing to participate and informed consent is obtained. Exclusion criteria
• Presence of alarm symptoms such as severe organic GI diseases, unexplained iron deficiency anaemia, unintentional weight loss, palpable abdominal mass.
• No active substance intake.

Conditions

Irritable Bowel Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: HEALTH_SERVICES_RESEARCH
• Blinding Strategy: DOUBLE

Study Groups

Experimental arms

Melatonin dose: 3mg/OD

Group Type: EXPERIMENTAL

Melatonin 3 mg

Intervention Type: DRUG

Melatonin dose: 3mg/OD Melatonin is a hormone made by the pineal gland; its biosynthesis is initiated by the uptake of the essential amino acid tryptophan and is an important inducer of sleep. Abnormality in melatonin has been shown in several studies on patients of IBS and functional constipation.

Control arms

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Similar looking placebo

Interventions

Melatonin 3 mg

Melatonin dose: 3mg/OD Melatonin is a hormone made by the pineal gland; its biosynthesis is initiated by the uptake of the essential amino acid tryptophan and is an important inducer of sleep. Abnormality in melatonin has been shown in several studies on patients of IBS and functional constipation.

Intervention Type: DRUG

Placebo

Similar looking placebo

Intervention Type: OTHER

Other Intervention Names

5-Methoxy-N-Acetyltryptamine

Eligibility Criteria

Inclusion Criteria

• Diagnosis by ROME III/IV criteria.
• Willing to participate and informed consent is obtained.

Exclusion Criteria

• Presence of alarm symptoms such as severe organic GI diseases, unexplained iron deficiency anemia, unintentional weight loss, palpable abdominal mass.
• No active substance intake.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Sanjay Gandhi Postgraduate Institute of Medical Sciences

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Uday C Ghoshal

Role: PRINCIPAL_INVESTIGATOR

Medical council of India, Association of Indian Universities

Locations

Department of Critical Care Medicine, SGPGIMS

Lucknow, Uttar Pradesh, India

Site Status: RECRUITING

Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS)

Lucknow, Uttar Pradesh, India

Site Status: NOT_YET_RECRUITING

Countries

India

Central Contacts

Uday C Ghoshal

Role: CONTACT

udayghoshal@gmail.com

05222494405

Facility Contacts

Mohan Gurjar, MD, PDCC

Role: primary

mohan@sgpgi.ac.in

91-522-2495403

Arvind K Baronia, MD

Role: backup

baronia@sgpgi.ac.in

91-522-2494540

Uday C Ghoshal

Role: primary

udayghoshal@gmail.com

05222494405

References

Ghoshal UC, Shukla A. Malnutrition in inflammatory bowel disease patients in northern India: frequency and factors influencing its development. Trop Gastroenterol. 2008 Apr-Jun;29(2):95-7.

Reference Type: RESULT

PMID: 18972769 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Informed Consent Form

View Document

Other Identifiers

2018-207-EMP-107

Identifier Type: -

Identifier Source: org_study_id