Inulin-Spirulina Co-intervention for Insomnia Disorder

This study is a single-center, prospective, randomized, double-blind, four-arm parallel-group clinical trial designed to evaluate the efficacy and safety of inulin and spirulina, administered alone or in combination, in adults with chronic insomnia disorder.

Insomnia disorder is associated with impaired sleep quality, emotional disturbances, and reduced cognitive function. Emerging evidence suggests that dysregulation of the gut microbiota and its metabolites may play an important role in the pathophysiology of sleep disorders through the gut-brain axis. Inulin, a prebiotic dietary fiber, and spirulina, a nutrient-rich microalga with anti-inflammatory and antioxidant properties, have both been shown to modulate gut microbiota composition and metabolic activity. Their combined use may produce synergistic effects on sleep regulation and related physiological processes.

In this study, eligible participants will be randomly assigned in a 1:1:1:1 ratio to receive inulin, spirulina, inulin plus spirulina, or placebo for 12 weeks. The interventions will be administered in powder form once daily, with identical appearance and packaging to ensure blinding of participants and study personnel.

The primary objective is to evaluate the effect of the interventions on sleep quality. Secondary objectives include assessing changes in sleep architecture, mood and anxiety symptoms, and cognitive function. In addition, this study aims to explore potential biological mechanisms by examining changes in gut microbiota composition before and after the intervention. Plasma samples collected at baseline and week 12 will be used for exploratory metabolomic analyses to further investigate potential biological pathways associated with treatment response.

Safety will be assessed throughout the study by monitoring adverse events. The findings of this study are expected to provide evidence on whether combined inulin and spirulina supplementation offers superior clinical benefits compared with single interventions or placebo, and to improve understanding of microbiota-related pathways involved in sleep regulation.

Inclusion criteria

• Aged 18 to 60 years;
• Meet the ICSD-3 diagnostic criteria for chronic insomnia disorder;
• Pittsburgh Sleep Quality Index (PSQI) total score > 5;
• Willing to participate and provide written informed consent.

Exclusion criteria

• Use of prebiotics, probiotics, high-fiber supplements, or microbiota-related products within the past 8 weeks;
• Diagnosis of psychiatric disorders other than insomnia based on DSM-5 criteria, assessed using the Mini-International Neuropsychiatric Interview (MINI);
• Regular use of sedative or hypnotic medications within the past 4 weeks, or frequent intermittent use (e.g., benzodiazepines, non-benzodiazepine receptor agonists, melatonin receptor agonists, sedating antihistamines);
• Severe hepatic or renal dysfunction, hematologic disorders, or respiratory diseases;
• Severe gastrointestinal diseases or malnutrition;
• Pregnancy or breastfeeding;
• Apnea-hypopnea index > 10, or periodic limb movement index > 15/hour on polysomnography;
• Known allergy or intolerance to inulin, spirulina, or maltodextrin;
• Participation in another clinical trial within the past 3 months.