Chronic Insomnia DisorderNCT06606938
FMT for Insomnia Disorder (FMT-SLEEP)
A study testing Faecal Microbiota Transplantation in people with Chronic Insomnia Disorder, run by Chinese University of Hong Kong at 1 site in Hong Kong.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Insomnia Disorder
- What is being tested?
- Faecal Microbiota Transplantation
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 74 participants
- Where
- 1 siteHong Kong
- Study dates
- 1 Nov 2024to 30 Apr 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 12Show fewer
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Faecal Microbiota Transplantation for Insomnia Disorder: a Randomized, Double-blind, Placebo-controlled Trial
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.
Read the 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
- Being tested
- Faecal Microbiota Transplantation, Normal Saline (Placebo)
- Keywords
- Faecal Microbiota Transplantation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Faecal Microbiota TransplantationProcedure or surgery
FMT at baseline, week 2, week 4
Normal Saline (Placebo)Procedure or surgery
Placebo at baseline, week 2, week 4
| Study group | Role | What they receive |
|---|---|---|
| Faecal Microbiota Transplantation | Experimental | FMT will be reconstituted from healthy donor's stool Receives: Procedure: Faecal Microbiota Transplantation |
| Placebo | Sham comparator | Subjects will receive 0.9% sodium chloride solution (normal saline) as placebo identical looking with FMT Receives: Procedure: Normal Saline (Placebo) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of subjects in remission
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
Measured: week 8
Secondary outcomes (13)
Proportion of subjects in remission
Proportion of subjects in remission (Insomnia Severity Index (ISI) below 8)
Measured: weeks 2, 4, and 24
Proportion of subjects with response
Proportion of subjects with response of a reduction of ISI above 6
Measured: weeks 2, 4, 8, and 24
Change in anxiety symptoms
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.
Measured: weeks 2, 4, 8, and 24
Change in depression symptoms
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.
Measured: weeks 2, 4, 8, and 24
Change in daytime sleepiness
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.
Measured: weeks 2, 4, 8, and 24
Change in sleep efficiency by actigraph
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.
Measured: weeks 8 and 24
Change in sleep pattern by sleep diary
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.
Measured: weeks 2, 4, 8, and 24
Change in Patient Global Impression - Improvement
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.
Measured: weeks 2, 4, 8, and 24
Change in quality of life
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.
Measured: weeks 8, and 24
Change in fatigue scale
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.
Measured: weeks 2, 4, 8, and 24
Change in sleep-related beliefs and attitudes
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.
Measured: weeks 2, 4, 8, and 24
Change in gut microbiota composition
Relative abundance of gut microbiota at species level will be assessed by metagenomic analysis.
Measured: week 8
Change in mucosal microbiota composition
Relative abundance of mucosal microbiota at species level will be assessed by metagenomic analysis.
Measured: week 4
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Sep 2024
- Study start1 Nov 2024 (estimated)
- Primary completion31 Oct 2026 (estimated)
- Study completion30 Apr 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (15)Papers the sponsor has linked to this study.
- Other trials for Chronic Insomnia DisorderStudies of the same condition, open and under way.
- More trials run by Chinese University of Hong KongThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- The intervention group will receive FMT while the control group will receive 0.9% sodium chloride solution (normal saline) as placebo.
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 74 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Chinese University of Hong Kong
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Siew Chien NG, Chinese University of Hong Kong
- Investigators
- Siew Chien Ng, PhD,FRCP, Principal investigator, Chinese University of Hong Kong
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06606938
- Sponsor's protocol ID
- FMT-SLEEP
- Status last verified
- Sep 2024
- First submitted
- 23 Aug 2024
- Last updated
- 23 Sep 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Buysse DJ. Insomnia. JAMA. 2013 Feb 20;309(7):706-16. doi: 10.1001/jama.2013.193.
PubMed 23423416K Pavlova M, Latreille V. Sleep Disorders. Am J Med. 2019 Mar;132(3):292-299. doi: 10.1016/j.amjmed.2018.09.021. Epub 2018 Oct 4.
PubMed 30292731Jahrami HA, Alhaj OA, Humood AM, Alenezi AF, Fekih-Romdhane F, AlRasheed MM, Saif ZQ, Bragazzi NL, Pandi-Perumal SR, BaHammam AS, Vitiello MV. Sleep disturbances during the COVID-19 pandemic: A systematic review, meta-analysis, and meta-regression. Sleep Med Rev. 2022 Apr;62:101591. doi: 10.1016/j.smrv.2022.101591. Epub 2022 Jan 22.
PubMed 35131664Sivertsen B, Lallukka T, Salo P, Pallesen S, Hysing M, Krokstad S, Simon Overland. Insomnia as a risk factor for ill health: results from the large population-based prospective HUNT Study in Norway. J Sleep Res. 2014 Apr;23(2):124-32. doi: 10.1111/jsr.12102.
PubMed 24635564Grandner MA. Sleep, Health, and Society. Sleep Med Clin. 2022 Jun;17(2):117-139. doi: 10.1016/j.jsmc.2022.03.001. Epub 2022 Apr 22.
PubMed 35659068Taddei-Allen P. Economic burden and managed care considerations for the treatment of insomnia. Am J Manag Care. 2020 Mar;26(4 Suppl):S91-S96. doi: 10.37765/ajmc.2020.43008.
PubMed 32282179Leger D, Bayon V. Societal costs of insomnia. Sleep Med Rev. 2010 Dec;14(6):379-89. doi: 10.1016/j.smrv.2010.01.003. Epub 2010 Mar 31.
PubMed 20359916Leach MJ, Page AT. Herbal medicine for insomnia: A systematic review and meta-analysis. Sleep Med Rev. 2015 Dec;24:1-12. doi: 10.1016/j.smrv.2014.12.003. Epub 2014 Dec 17.
PubMed 25644982Pan B, Ge L, Lai H, Hou L, Tian C, Wang Q, Yang K, Lu Y, Zhu H, Li M, Wang D, Li X, Zhang Y, Gao Y, Liu M, Ding G, Tian J, Yang K. The Comparative Effectiveness and Safety of Insomnia Drugs: A Systematic Review and Network Meta-Analysis of 153 Randomized Trials. Drugs. 2023 May;83(7):587-619. doi: 10.1007/s40265-023-01859-8. Epub 2023 Mar 22.
PubMed 36947394De Crescenzo F, D'Alo GL, Ostinelli EG, Ciabattini M, Di Franco V, Watanabe N, Kurtulmus A, Tomlinson A, Mitrova Z, Foti F, Del Giovane C, Quested DJ, Cowen PJ, Barbui C, Amato L, Efthimiou O, Cipriani A. Comparative effects of pharmacological interventions for the acute and long-term management of insomnia disorder in adults: a systematic review and network meta-analysis. Lancet. 2022 Jul 16;400(10347):170-184. doi: 10.1016/S0140-6736(22)00878-9.
PubMed 35843245Qaseem A, Kansagara D, Forciea MA, Cooke M, Denberg TD; Clinical Guidelines Committee of the American College of Physicians. Management of Chronic Insomnia Disorder in Adults: A Clinical Practice Guideline From the American College of Physicians. Ann Intern Med. 2016 Jul 19;165(2):125-33. doi: 10.7326/M15-2175. Epub 2016 May 3.
PubMed 27136449Riemann D, Espie CA, Altena E, Arnardottir ES, Baglioni C, Bassetti CLA, Bastien C, Berzina N, Bjorvatn B, Dikeos D, Dolenc Groselj L, Ellis JG, Garcia-Borreguero D, Geoffroy PA, Gjerstad M, Goncalves M, Hertenstein E, Hoedlmoser K, Hion T, Holzinger B, Janku K, Jansson-Frojmark M, Jarnefelt H, Jernelov S, Jennum PJ, Khachatryan S, Krone L, Kyle SD, Lancee J, Leger D, Lupusor A, Marques DR, Nissen C, Palagini L, Paunio T, Perogamvros L, Pevernagie D, Schabus M, Shochat T, Szentkiralyi A, Van Someren E, van Straten A, Wichniak A, Verbraecken J, Spiegelhalder K. The European Insomnia Guideline: An update on the diagnosis and treatment of insomnia 2023. J Sleep Res. 2023 Dec;32(6):e14035. doi: 10.1111/jsr.14035.
PubMed 38016484Riemann D, Baglioni C, Bassetti C, Bjorvatn B, Dolenc Groselj L, Ellis JG, Espie CA, Garcia-Borreguero D, Gjerstad M, Goncalves M, Hertenstein E, Jansson-Frojmark M, Jennum PJ, Leger D, Nissen C, Parrino L, Paunio T, Pevernagie D, Verbraecken J, Weess HG, Wichniak A, Zavalko I, Arnardottir ES, Deleanu OC, Strazisar B, Zoetmulder M, Spiegelhalder K. European guideline for the diagnosis and treatment of insomnia. J Sleep Res. 2017 Dec;26(6):675-700. doi: 10.1111/jsr.12594. Epub 2017 Sep 5.
PubMed 28875581Lau RI, Su Q, Ching JYL, Lui RN, Chan TT, Wong MTL, Lau LHS, Wing YK, Chan RNY, Kwok HYH, Ho AHY, Tse YK, Cheung CP, Li MKT, Siu WY, Liu C, Lu W, Wang Y, Chiu EOL, Cheong PK, Chan FKL, Ng SC. Fecal Microbiota Transplantation for Sleep Disturbance in Post-acute COVID-19 Syndrome. Clin Gastroenterol Hepatol. 2024 Dec;22(12):2487-2496.e6. doi: 10.1016/j.cgh.2024.06.004. Epub 2024 Jun 20.
PubMed 38908733Fang H, Yao T, Li W, Pan N, Xu H, Zhao Q, Su Y, Xiong K, Wang J. Efficacy and safety of fecal microbiota transplantation for chronic insomnia in adults: a real world study. Front Microbiol. 2023 Nov 21;14:1299816. doi: 10.3389/fmicb.2023.1299816. eCollection 2023.
PubMed 38088972
Study at a glance
From the registry record, last updated by the sponsor on 23 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Faecal Microbiota Transplantation for Insomnia Disorder: a Randomized, Double-blind, Placebo-controlled Trial
- ClinicalTrials.gov ID
- NCT06606938
- Acronym / sponsor ID
- FMT-SLEEP
- Conditions
- Chronic Insomnia Disorder
- Keywords
- Faecal Microbiota Transplantation
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 74 participants (estimated)
- Lead sponsor
- Chinese University of Hong KongUniversity, hospital or other
- Study start
- 1 Nov 2024 (estimated)
- Primary completion
- 31 Oct 2026 (estimated)
- Study completion
- 30 Apr 2027 (estimated)
- First posted
- 23 Sep 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
- Model description
- The intervention group will receive FMT while the control group will receive 0.9% sodium chloride solution (normal saline) as placebo.
| Arm | Type | Receives |
|---|---|---|
| Faecal Microbiota Transplantation | Experimental | Procedure: Faecal Microbiota TransplantationFMT will be reconstituted from healthy donor's stool |
| Placebo | Sham comparator | Procedure: Normal Saline (Placebo)Subjects will receive 0.9% sodium chloride solution (normal saline) as placebo identical looking with FMT |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Faecal Microbiota TransplantationFMT at baseline, week 2, week 4 | Procedure or surgery | Faecal Microbiota Transplantation |
| Normal Saline (Placebo)Placebo at baseline, week 2, week 4 | Procedure or surgery | Placebo |
Primary outcome
Proportion of subjects in remission
Time frame: 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
13 secondary outcomes
Proportion of subjects in remission
Time frame: weeks 2, 4, and 24
Proportion of subjects with response
Time frame: weeks 2, 4, 8, and 24
Change in anxiety symptoms
Time frame: weeks 2, 4, 8, and 24
Change in depression symptoms
Time frame: weeks 2, 4, 8, and 24
Change in daytime sleepiness
Time frame: weeks 2, 4, 8, and 24
Change in sleep efficiency by actigraph
Time frame: weeks 8 and 24
Change in sleep pattern by sleep diary
Time frame: weeks 2, 4, 8, and 24
Change in Patient Global Impression - Improvement
Time frame: weeks 2, 4, 8, and 24
Change in quality of life
Time frame: weeks 8, and 24
Change in fatigue scale
Time frame: weeks 2, 4, 8, and 24
Change in sleep-related beliefs and attitudes
Time frame: weeks 2, 4, 8, and 24
Change in gut microbiota composition
Time frame: week 8
Change in mucosal microbiota composition
Time frame: week 4
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Sep 2024.
- Background: PubMed 23423416Buysse DJ. Insomnia. JAMA. 2013 Feb 20;309(7):706-16. doi: 10.1001/jama.2013.193.
- Background: PubMed 30292731K Pavlova M, Latreille V. Sleep Disorders. Am J Med. 2019 Mar;132(3):292-299. doi: 10.1016/j.amjmed.2018.09.021. Epub 2018 Oct 4.
- Background: PubMed 35131664Jahrami HA, Alhaj OA, Humood AM, Alenezi AF, Fekih-Romdhane F, AlRasheed MM, Saif ZQ, Bragazzi NL, Pandi-Perumal SR, BaHammam AS, Vitiello MV. Sleep disturbances during the COVID-19 pandemic: A systematic review, meta-analysis, and meta-regression. Sleep Med Rev. 2022 Apr;62:101591. doi: 10.1016/j.smrv.2022.101591. Epub 2022 Jan 22.
- Background: PubMed 24635564Sivertsen B, Lallukka T, Salo P, Pallesen S, Hysing M, Krokstad S, Simon Overland. Insomnia as a risk factor for ill health: results from the large population-based prospective HUNT Study in Norway. J Sleep Res. 2014 Apr;23(2):124-32. doi: 10.1111/jsr.12102.
- Background: PubMed 35659068Grandner MA. Sleep, Health, and Society. Sleep Med Clin. 2022 Jun;17(2):117-139. doi: 10.1016/j.jsmc.2022.03.001. Epub 2022 Apr 22.
- Background: PubMed 32282179Taddei-Allen P. Economic burden and managed care considerations for the treatment of insomnia. Am J Manag Care. 2020 Mar;26(4 Suppl):S91-S96. doi: 10.37765/ajmc.2020.43008.
- Background: PubMed 20359916Leger D, Bayon V. Societal costs of insomnia. Sleep Med Rev. 2010 Dec;14(6):379-89. doi: 10.1016/j.smrv.2010.01.003. Epub 2010 Mar 31.
- Background: PubMed 25644982Leach MJ, Page AT. Herbal medicine for insomnia: A systematic review and meta-analysis. Sleep Med Rev. 2015 Dec;24:1-12. doi: 10.1016/j.smrv.2014.12.003. Epub 2014 Dec 17.
- Background: PubMed 36947394Pan B, Ge L, Lai H, Hou L, Tian C, Wang Q, Yang K, Lu Y, Zhu H, Li M, Wang D, Li X, Zhang Y, Gao Y, Liu M, Ding G, Tian J, Yang K. The Comparative Effectiveness and Safety of Insomnia Drugs: A Systematic Review and Network Meta-Analysis of 153 Randomized Trials. Drugs. 2023 May;83(7):587-619. doi: 10.1007/s40265-023-01859-8. Epub 2023 Mar 22.
- Background: PubMed 35843245De Crescenzo F, D'Alo GL, Ostinelli EG, Ciabattini M, Di Franco V, Watanabe N, Kurtulmus A, Tomlinson A, Mitrova Z, Foti F, Del Giovane C, Quested DJ, Cowen PJ, Barbui C, Amato L, Efthimiou O, Cipriani A. Comparative effects of pharmacological interventions for the acute and long-term management of insomnia disorder in adults: a systematic review and network meta-analysis. Lancet. 2022 Jul 16;400(10347):170-184. doi: 10.1016/S0140-6736(22)00878-9.
- Background: PubMed 27136449Qaseem A, Kansagara D, Forciea MA, Cooke M, Denberg TD; Clinical Guidelines Committee of the American College of Physicians. Management of Chronic Insomnia Disorder in Adults: A Clinical Practice Guideline From the American College of Physicians. Ann Intern Med. 2016 Jul 19;165(2):125-33. doi: 10.7326/M15-2175. Epub 2016 May 3.
- Background: PubMed 38016484Riemann D, Espie CA, Altena E, Arnardottir ES, Baglioni C, Bassetti CLA, Bastien C, Berzina N, Bjorvatn B, Dikeos D, Dolenc Groselj L, Ellis JG, Garcia-Borreguero D, Geoffroy PA, Gjerstad M, Goncalves M, Hertenstein E, Hoedlmoser K, Hion T, Holzinger B, Janku K, Jansson-Frojmark M, Jarnefelt H, Jernelov S, Jennum PJ, Khachatryan S, Krone L, Kyle SD, Lancee J, Leger D, Lupusor A, Marques DR, Nissen C, Palagini L, Paunio T, Perogamvros L, Pevernagie D, Schabus M, Shochat T, Szentkiralyi A, Van Someren E, van Straten A, Wichniak A, Verbraecken J, Spiegelhalder K. The European Insomnia Guideline: An update on the diagnosis and treatment of insomnia 2023. J Sleep Res. 2023 Dec;32(6):e14035. doi: 10.1111/jsr.14035.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Siew Chien Ng, PhD,FRCP principal investigator
Chinese University of Hong Kong
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Faecal Microbiota Transplantation in people with Chronic Insomnia Disorder, run by Chinese University of Hong Kong at 1 site in Hong Kong.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 23 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Hong Kong. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Yun Wang (85235051519, 1155202358@link.cuhk.edu.hk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of subjects in remission (time frame: week 8). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06606938, which also lists 15 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Sep 2024.