FMT for Insomnia Disorder (FMT-SLEEP)

NCT ID: NCT06606938

Last Updated: 2024-09-23

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 74 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-11-01
• Study Completion Date: 2027-04-30

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.

Conditions

Chronic Insomnia Disorder

Study Design

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

Study Groups

Faecal Microbiota Transplantation

FMT will be reconstituted from healthy donor's stool

Group Type: EXPERIMENTAL

Faecal Microbiota Transplantation

Intervention Type: PROCEDURE

FMT at baseline, week 2, week 4

Placebo

Subjects will receive 0.9% sodium chloride solution (normal saline) as placebo identical looking with FMT

Group Type: SHAM_COMPARATOR

Normal Saline (Placebo)

Intervention Type: PROCEDURE

Placebo at baseline, week 2, week 4

Interventions

Faecal Microbiota Transplantation

FMT at baseline, week 2, week 4

Intervention Type: PROCEDURE

Normal Saline (Placebo)

Placebo at baseline, week 2, week 4

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• 1. Individuals aged 18 and above
• 2. 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

Exclusion Criteria

• 1. 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)
• 2. Requiring immediate psychiatric care (e.g., imminently suicidal subjects) or have attempted suicide in the past 6 months
• 3. Change of treatment or therapy for insomnia within 4 weeks
• 4. Known history of severe organ failure (including decompensated cirrhosis), renal failure on dialysis, suffering from human immunodeficiency virus infection
• 5. Confirmed active malignancy
• 6. Had abdominal surgery
• 7. Contraindications to GI endoscopy
• 8. On shift work
• 9. Taking antibiotics, probiotic or prebiotic preparations within 4 weeks
• 10. Known pregnancy
• 11. Mental retardation or inability to provide informed consent
• 12. Are participating in other interventional studies

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chinese University of Hong Kong

OTHER

Sponsor Role: lead

Responsible Party

Siew Chien NG

Professor Siew Chien NG

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Siew Chien Ng, PhD,FRCP

Role: PRINCIPAL_INVESTIGATOR

Chinese University of Hong Kong

Locations

Prince of Wales Hospital

Hong Kong, , Hong Kong

Countries

Hong Kong

Central Contacts

Yun Wang

Role: CONTACT

1155202358@link.cuhk.edu.hk

85235051519

Jessica Ching, PhD

Role: CONTACT

jessicaching@cuhk.edu.hk

85235053524

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Other Identifiers

FMT-SLEEP

Identifier Type: -

Identifier Source: org_study_id