FMT for Insomnia Disorder (FMT-SLEEP)
- Conditions
- Chronic Insomnia Disorder
- Interventions
- Procedure: Faecal Microbiota TransplantationProcedure: Normal Saline (Placebo)
- Registration Number
- NCT06606938
- Lead Sponsor
- Chinese University of Hong Kong
- Brief Summary
Insomnia disorder is characterized by difficulty initiating or maintaining sleep, or early morning awakening accompanied by symptoms such as irritability or fatigue during wakefulness. It is one of the most prevalent health concerns in the population and in clinical practice, with more than one-third of adults experience transient insomnia at some point in their lives. In about 40% of cases, insomnia can develop into a more chronic condition. The COVID-19 pandemic has further aggravated sleep problems, with a reported global prevalence of sleep disturbances reaching 40-49%. The implications of insomnia disorder are substantial, encompassing social, economic, psychological, and physical aspects.
Behavioural, cognitive, and pharmacological interventions can all be effective for insomnia. Pharmacological treatment is commonly used but may have drawbacks such as adverse events and inconclusive safety data for certain medications. Many licensed drugs can be effective in the acute treatment of insomnia but are associated with poor tolerability, or information about long-term effects is not available. Alternatively, cognitive behavioural therapy for insomnia (CBT-I), has been recommended as the first-line treatment for chronic insomnia in adults of any age according to the American and European guidelines. But issue of accessibility, compliance/adherence, and moderate response limit the practicality and applicability of CBT-I.
Recent evidence suggests that the gut microbiota plays a role in regulating sleep behaviour, both directly and indirectly. This has led to the exploration of gut microbiota modulation as a potential therapy for insomnia. Faecal microbiota transplantation (FMT), which is the infusion of faeces from healthy donors to the gut of affected subjects, has shown impressive therapeutic effects for various diseases. Several real-world studies have demonstrated improvements in symptoms of insomnia disorder following FMT. One previous study also indicated the potential of FMT in alleviating post-COVID insomnia. In this randomised, double-blind, placebo-controlled trial, the investigators aim to assess the efficacy of FMT in improving insomnia disorder. Two groups will be recruited in 1:1 ratio. The intervention group will receive FMT while the control group will receive normal saline as placebo. Both groups will have the same assessments.
- Detailed Description
Insomnia disorder is characterized by difficulty initiating or maintaining sleep, or early morning awakening accompanied by daytime symptoms such as irritability or fatigue. It is one of the most prevalent health problems in the population and in clinical practice, with more than one-third of adults experience transient insomnia at some point in their lives. In about 40% of cases, insomnia can develop into a more chronic condition. The COVID-19 pandemic has further aggravated sleep problems, with a reported global prevalence of sleep disturbances reaching 40-49%. The social, economic, psychological and physical implications of insomnia disorder are substantial, with evidence linking the condition to an increased risk of hypertension, cardiovascular disease, anxiety, and depression, as well as impaired quality of life, work absenteeism, work-related accidents, poor work efficiency, and family dysfunction.
Behavioural, cognitive, and pharmacological interventions can all be effective for insomnia. Pharmacological treatment is common in practice and widely used for the management of insomnia. A recent meta-analysis suggested that Eszopiclone and Lemborexant had the best profile in terms of efficacy, acceptability, and tolerability. However, Eszopiclone might cause substantial adverse events and safety data on lemborexant were inconclusive. Many licensed drugs (including benzodiazepines, Z-hypnotics and dual orexin receptor antagonist, DORA) are prescribed as effective short-term treatment of insomnia but some are associated with poor tolerability, or the information about long-term safety effects is not available. Alternatively, cognitive behavioral therapy for insomnia (CBT-I), has been recommended as the first-line treatment for chronic insomnia in adults of any age according to the American and European guidelines. But issues of accessibility, compliance/adherence, and moderate response also pose limit the practicality and applicability of CBT-I.
Growing evidence indicates that the microbiota-gut-brain axis contributes to the regulation of sleep behavior both directly and indirectly and may play a critical role in the etiology and pathogenesis of sleep disorders. Sleep loss is capable of altering the gut microbiota composition through increased hunger and decreased physical activity, immunomodulation, or hypothalamus-pituitary-adrenal (HPA) axis activation and subsequent intestinal barrier disruption. Conversely, the gut microbiome is capable of altering sleep through somnogenic lipopolysaccharide (LPS) and Muramyl peptides translocation, vagal afferent excitation in response to enteric LPS, regulation of enterochromaffin cell serotonin production, and inflammatory cytokine regulation. Consequently, gut microbiota modulation is a potential therapy for insomnia.
According to a preclinical study, transplantation of the gut microbiota from mice with sleep disorder into normal mice induced microglia overactivation and neuronal apoptosis in the hippocampus, cognitive decline, and colonic microbiota disorder. Moreover, a human study found that fecal microbiota transplantation (FMT) from healthy donors improved sleep and also ameliorated depression and anxiety in patients with irritable bowel syndrome (IBS). Another study demonstrated that FMT led to a decrease in the scores of the five components of Pittsburgh Sleep Quality Index (PSQI) in 52 IBS patients with poor sleep quality, including subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, and sleep disturbances. A clinical study showed significantly lower Sleep Disturbance Scale for Children (SDSC) scores in children with autism after FMT, whilst a retrospective study also indicated that FMT could significantly improve the sleep disorder scores in the autistic children with constipation. According to a real world study, FMT significantly ameliorated the Insomnia Severity Index (ISI), Pittsburgh Sleep Quality Index (PSQI), and quality of life in patients with chronic insomnia. The results from one previous study also demonstrated that FMT could alleviate post-COVID insomnia.
In this randomised, double-blind, placebo-controlled trial, the investigators aim to assess the efficacy of FMT in improving insomnia disorder. The investigators hypothesize that FMT is a safe and effective treatment for insomnia disorder.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 74
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- Individuals aged 18 and above
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- Subjects who were diagnosed with chronic insomnia disorder according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) and with moderate or above insomnia disorder defined as ISI > 14
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- Having an additional sleep disorder, such as restless legs syndrome, or circadian rhythm sleep disorder, that can significantly disrupt the sleep cycle as ascertained by Diagnostic Interview for Sleep Patterns and Disorders (DISP)
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- Requiring immediate psychiatric care (e.g., imminently suicidal subjects) or have attempted suicide in the past 6 months
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- Change of treatment or therapy for insomnia within 4 weeks
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- Known history of severe organ failure (including decompensated cirrhosis), renal failure on dialysis, suffering from human immunodeficiency virus infection
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- Confirmed active malignancy
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- Had abdominal surgery
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- Contraindications to GI endoscopy
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- On shift work
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- Taking antibiotics, probiotic or prebiotic preparations within 4 weeks
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- Known pregnancy
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- Mental retardation or inability to provide informed consent
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- Are participating in other interventional studies
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Faecal Microbiota Transplantation Faecal Microbiota Transplantation FMT will be reconstituted from healthy donor's stool Placebo Normal Saline (Placebo) Subjects will receive 0.9% sodium chloride solution (normal saline) as placebo identical looking with FMT
- Primary Outcome Measures
Name Time Method Proportion of subjects in remission week 8 Proportion of subjects in remission (Insomnia Severity Index (ISI) \< 8) by week 8. ISI is a self-report questionnaire used to evaluate the nature, severity and impact of insomnia. Total score ranges from 0 to 28. Higher score indicates more severe insomnia
- Secondary Outcome Measures
Name Time Method Proportion of subjects in remission weeks 2, 4, and 24 Proportion of subjects in remission (Insomnia Severity Index (ISI) below 8)
Proportion of subjects with response weeks 2, 4, 8, and 24 Proportion of subjects with response of a reduction of ISI above 6
Change in anxiety symptoms weeks 2, 4, 8, and 24 Anxiety symptoms will be assessed by a 7-item Generalised Anxiety Disorder-7 scale (GAD-7). GAD-7 is a widely used diagnostic self-report scale for the screening, diagnosis and severity assessment of anxiety disorder. Total score ranges from 0 to 21. Higher score indicates more severe anxiety.
Change in depression symptoms weeks 2, 4, 8, and 24 Depresion symptoms will be evaluated by the Patient Health Questionnaire-9 (PHQ-9), a 9-item instrument. Total score categories for PHQ-9 are: 0-4 = Minimal/no depression, 5-9 = Mild depression, 10-14 = Moderate depression, 15-19 = Moderately severe depression, 20-27 = Severe depression.
Change in daytime sleepiness weeks 2, 4, 8, and 24 Daytime sleepiness will be measured by using the Epworth Sleepiness Scale (ESS). The ESS consists of eight situations in which individuals rate their likelihood of nodding off on a scale of 0 to 3, where 0 represents "Would Never Nod Off" and 3 represents "High Chance of Nodding Off". To obtain a total score on the ESS, the scores for each of the eight situations are summed, resulting in a range from 0 to 24. Higher scores indicate a higher level of daytime sleepiness.
Change in sleep efficiency by actigraph weeks 8 and 24 Actigraph is a non-invasive method used to monitor and measure activity levels and sleep patterns over a period. It contains an accelerometer that measures activity and provides data on the intensity, duration, and frequency of physical movements. Sleep and wake status will be determined by algoraithm that calculate activity count measured by the accelerometer. Bedtime, wakeup time, sleep duration, sleep onset latency and sleep efficiency will be generated.
Change in sleep pattern by sleep diary weeks 2, 4, 8, and 24 The Sleep Diary is also utilised to record the quality and quantity of subjects' sleep. A sleep diary is a tool used to track and record various aspects of an individual's sleep patterns and habits over a period of time. It provides a detailed account of sleep-related information that can be helpful for assessing sleep quality, identifying patterns or issues, and guiding treatment or behavior modifications. The sleep diary will include the following information: Date, Bedtime, Sleep onset, Wake-up time, Sleep duration, Number of awakenings, Sleep quality, Napping, and Comments.
Change in Patient Global Impression - Improvement weeks 2, 4, 8, and 24 The Patient Global Impression-Improvement (PGI-I) will be used to assess subjects' perceptions regarding the effects of study invention on their sleep. The PGI-I scale consists of a single question that asks the patient to rate their improvement since the start of the study invention, using a seven-point scale ranging from very much improved to very much worse.
Change in quality of life weeks 8, and 24 The quality of life of subjects will be evaluated via 12-item Short Form Survey (SF-12) covering eight domains: Limitations in physical activities because of health problems; Limitations in social activities because of physical or emotional problems; Limitations in usual role activities because of physical health problems; Bodily pain; General mental health (psychological distress and well-being); Limitations in usual role activities because of emotional problems; Vitality (energy and fatigue); General health perceptions. The SF-12 provides two summary scores: the Physical Component Summary (PCS) score and the Mental Component Summary (MCS) score. Both summary scores are calculated based on a standardized scoring algorithm, which assigns weights to each of the 12 items and combines the responses to generate a score. A higher PCS score suggests better physical health functioning and a higher MCS score represents better mental health.
Change in fatigue scale weeks 2, 4, 8, and 24 The Multidimensional Fatigue Inventory (MFI) will be used to evaluate subjects' fatigue. The MFI is a 20-item scale designed to evaluate five dimensions of fatigue: general fatigue, physical fatigue, reduced motivation, reduced activity, and mental fatigue. For each item, subjects rate their experience of fatigue on a scale, ranging from 1 to 5. Higher scores indicate higher levels of fatigue within each subscale. The total score for each subscale is typically obtained by summing the scores of the corresponding items.
Change in sleep-related beliefs and attitudes weeks 2, 4, 8, and 24 Subjects' beliefs and attitudes towards sleep will be assessed by the Dysfunctional Beliefs and Attitudes About Sleep Scale (DBAS)-16. Subjects rate their agreement with each item on a Likert scale, ranging from 1 to 10. Higher scores indicate a greater presence of dysfunctional beliefs and attitudes related to sleep.
Change in gut microbiota composition week 8 Relative abundance of gut microbiota at species level will be assessed by metagenomic analysis.
Change in mucosal microbiota composition week 4 Relative abundance of mucosal microbiota at species level will be assessed by metagenomic analysis.
Trial Locations
- Locations (1)
Prince of Wales Hospital
ðŸ‡ðŸ‡°Hong Kong, Hong Kong