Phase-specific fever management (ie, tailoring care to the rising, plateau and defevering stages of fever) and the cautious use of evidence-based natural medicinal products (NMPs, eg, herbal preparations with demonstrated evidence of safety and effectiveness) are hypothesised to reduce antibiotic (AB) use for acute, uncomplicated upper respiratory tract infections (URTIs). The objective of the trial is to investigate the effects of a parental phase-specific FeverApp and an NMP WebApp on AB use, the number of primary care visits and the gut microbiota of children with acute, uncomplicated URTIs.

The study design is a randomised controlled trial with three arms: a FeverApp group, an NMP WebApp group and a control group. Participants are parents of children aged 3 months to 12 years with fever (≥38°C) and symptoms of an acute, uncomplicated URTI. Parents (n=320) will complete a baseline questionnaire and collect a baseline stool sample from their child. The intervention groups then use one of the apps, and all parents report URTI symptoms of their child on days 2, 5 and 7. On day 10, they complete a follow-up questionnaire, and they collect a second stool sample from their child. The FeverApp contains evidence-based information about fever and how to manage it, tailored fever advice and an option to monitor a child’s health status during a fever episode. The NMP WebApp is an evidence-based online decision-making tool that helps parents navigate the use of NMPs with reported safety and effectiveness for URTI symptoms. The primary endpoint is AB use, and secondary endpoints include recovery time, complications/adverse events, the number of primary care visits/telephone consultations and changes in gut microbiota composition. Participants were recruited nationwide (urban and rural) via online advertising and community flyers.

A waiver was obtained from a recognised Institutional Review Board, participants signed for informed consent, and all data are pseudonymised and stored securely. Results will be published in scientific, peer-reviewed journals.

NCT06140446 (www.clinicaltrials.gov).

Functional constipation (FC) is prevalent among children and often persists despite standard pharmacological treatment with oral laxatives. Many parents turn to complementary therapies, including acupuncture, which has been shown to relieve symptoms in adults with FC. However, studies in children with FC are scarce and have important limitations. This study will evaluate the feasibility, safety and potential efficacy of acupuncture for children with FC.

Prospective, non-randomised, open-label pilot study in children with FC (6–18 years). Participants will undergo eight acupuncture sessions over 10 weeks. Concurrent pharmacological treatment with polyethylene glycol (≥0.2 g/kg/day) will continue as initiated prior to enrolment. The primary endpoint is feasibility, defined by an attrition rate of ≥70%. Secondary feasibility endpoints include consent rate, patient/parent satisfaction and personnel requirements. Safety will be assessed by systematic monitoring of adverse events. Efficacy endpoints include treatment success, defined as no longer meeting the Rome IV criteria for FC at the end of the intervention period, as well as defecation frequency, stool consistency, painful defecation, faecal incontinence frequency, abdominal pain, medication use and quality of life, based on a previously published core outcome set.

Ethical approval was provided by the Medical Ethics Committee of Amsterdam UMC (Netherlands; NL87083.018.24). Results will be published in peer-reviewed journals and presented to scientific and consumer audiences.

NCT06836362 and NL-OMON57236.

Major depressive disorder (MDD) is a severe mental health condition that profoundly affects both psychological and physical well-being. Growing evidence indicates that targeting the gut-brain axis could present new therapeutic opportunities for MDD, given the role of gut microbiota and their metabolites in its pathophysiology. One promising approach involves supplementation with butyrate, a short-chain fatty acid that has demonstrated antidepressant potential in preclinical models of depression. However, clinical research exploring the effects of butyrate supplementation in individuals with MDD remains lacking.

This study is a double-blind, parallel, 1:1 randomised placebo-controlled trial. The primary aim of this pilot study is to assess the feasibility and acceptability of an 8-week oral supplementation with tributyrin, a triglyceride form of butyrate (4 g/day), added to usual treatment with antidepressant medication in 24 patients with mild-to-severe MDD aged 18–65 years. Secondary outcomes include changes in depressive symptoms, assessed weekly throughout the supplementation period and at 16 weeks post-supplementation during follow-up, as well as changes in anhedonia and affect, measured multiple times per day via a smartphone application throughout the supplementation period. Additional outcomes include changes in gastrointestinal symptoms, changes in faecal microbiome, metabolites in blood and faeces, inflammation, epigenetic markers, stress and intestinal permeability.

The study has been approved by the Medical Research Ethics Committee of the Amsterdam University Medical Centre, the Netherlands.

Should the pilot demonstrate feasibility and acceptability, a larger-scale study will be warranted to evaluate the efficacy of tributyrin supplementation in alleviating depressive symptoms. This pilot will provide valuable insights to guide sample size calculations and refine study design for subsequent trials. Ultimately, this research could lead to novel adjunctive treatments for MDD targeting gut-brain signalling, offering new therapeutic avenues for patients with MDD.

This trial has been registered in the International Clinical Trials Registry Platform (registry number: NL-OMON57116).