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NCT Number: NCT07577089

Cognitive Behavioral Therapy for Functional Dyspepsia (Epigastric Pain Syndrome and Postprandial Distress Syndrome Subtypes)

The goal of this clinical trial is to learn whether adding Cognitive Behavioral Therapy (CBT) to standard medical treatment can improve symptoms in adults with Functional Dyspepsia. The study includes adults aged 18 to 65 years diagnosed with Functional Dyspepsia, classified as Epigastric Pain Syndrome or Postprandial Distress Syndrome.

The main questions it aims to answer are:

Does Cognitive Behavioral Therapy added to standard treatment reduce gastrointestinal symptoms compared with standard treatment alone? Do patients with Postprandial Distress Syndrome and Epigastric Pain Syndrome respond differently to Cognitive Behavioral Therapy? Researchers will compare optimized standard medical treatment alone to optimized standard treatment combined with Cognitive Behavioral Therapy to see if the addition of CBT leads to greater symptom improvement and better quality of life.

Participants will:

Be randomly assigned to receive either standard medical treatment alone or standard treatment plus Cognitive Behavioral Therapy Take part in clinical visits and complete questionnaires about gastrointestinal symptoms, psychological well-being, and quality of life Provide blood, saliva, and stool samples at several time points over a 12-month follow-up period

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Key information

Conditions

Functional Dyspepsia Epigastric Pain Syndrome Inflammation Pathologic Processes Pathological Conditions, Signs and Symptoms Postprandial Distress Syndrome

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

About this study

Functional Dyspepsia is a chronic disorder of gut-brain interaction characterized by persistent upper gastrointestinal symptoms in the absence of structural disease. It is commonly classified into Epigastric Pain Syndrome and Postprandial Distress Syndrome, which may reflect partially distinct underlying mechanisms. Standard medical treatments often provide incomplete symptom relief, and growing evidence supports a role for psychological factors and gut-brain axis dysregulation in symptom generation and persistence.

This randomized controlled trial investigates the effectiveness of adding a manualized Cognitive Behavioral Therapy program to optimized standard medical treatment in adults with Functional Dyspepsia. Participants are stratified by dyspepsia subtype and randomly assigned in a 1:1 ratio to receive either optimized standard treatment alone or optimized standard treatment combined with Cognitive Behavioral Therapy. Outcome assessors are blinded to treatment allocation.

The Cognitive Behavioral Therapy intervention is delivered individually by trained therapists and focuses on psychoeducation, cognitive restructuring, stress management, coping strategies, and behavioral and interoceptive exposure. The intervention is designed to target symptom-related cognitions, emotional responses, and behavioral patterns that may contribute to symptom persistence.

In addition to evaluating clinical efficacy, the study adopts a multimodal approach to characterize biological, psychological, and clinical factors associated with treatment response. Data collection includes clinical and psychological assessments and the collection of biological samples to explore markers related to inflammation, stress regulation, gut barrier function, and gut microbiota composition and activity. Measurements are obtained at baseline and during follow-up to assess changes over time and their relationship with symptom improvement.

The study aims to identify predictors of response to Cognitive Behavioral Therapy and to explore differences between Epigastric Pain Syndrome and Postprandial Distress Syndrome. By integrating clinical, psychological, and biological data, the trial seeks to support a more personalized treatment approach for Functional Dyspepsia and to improve the targeting of psychological interventions in clinical practice.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Age 18-65 years
  • Diagnosis of Functional Dyspepsia according to Rome IV criteria
  • Classification as Epigastric Pain Syndrome (EPS) or Postprandial Distress Syndrome (PDS)
  • Active symptoms within the last month
  • Willingness to participate in Cognitive Behavioral Therapy and provide biological samples for research
  • Ability to provide written informed consent

Exclusion criteria

  • Presence of structural gastrointestinal disease (e.g., peptic ulcer, malignancy)
  • History of major abdominal surgery affecting the stomach or small intestine
  • Severe psychiatric disorders (e.g., psychosis, bipolar disorder) interfering with participation
  • Current participation in other interventional clinical trials
  • Use of medications that may confound study outcomes (e.g., chronic corticosteroids, immunosuppressants)
  • Pregnancy or breastfeeding

Treatment and study plan

Optimized Standard Treatment (OPT)

Drug

Participants receive guideline-based standard medical treatment for Functional Dyspepsia, including proton pump inhibitors, antiacids, and prokinetics at recommended doses. This intervention does not include any psychological or behavioral therapy.

Cognitive Behavioral Therapy + Optimized Standard Treatment (CBT + OPT)

Behavioral

Participants receive the same optimized standard medical treatment as the OPT arm, plus a manualized Cognitive Behavioral Therapy program. CBT consists of 10 individual sessions (60 minutes each) over 12 weeks, with a 6-month booster session. Sessions cover psychoeducation, cognitive restructuring, stress management, coping strategies, interoceptive/behavioral exposure, relaxation, and nutritional integration.

Primary outcomes

  1. Reduction in gastrointestinal symptom severity as assessed by the Leeds Dyspepsia Questionnaire - Short Form (LDQ-SF)

    Time frame: Baseline (T0), 3 months (T1 - end of intervention), 6 months (T2 - intermediate follow-up), 12 months (T3 - final follow-up)

    The primary outcome is a statistically significant reduction in total LDQ-SF score in patients treated with CBT + optimized pharmacological treatment (OPT) compared to OPT alone, with an expected greater benefit in the Postprandial Distress Syndrome (PDS) subtype compared to the Epigastric Pain Syndrome (EPS) subtype. The LDQ-SF assesses the frequency and severity of dyspeptic symptoms (epigastric pain, heartburn, nausea, vomiting, early satiety, bloating, regurgitation, postprandial discomfort); scores range from 0 to 32, with higher scores indicating greater symptom severity. Responder status is defined as a ≥30-50% reduction in total LDQ-SF score from baseline.

Secondary outcomes

  1. Anxiety and Depression - Hospital Anxiety and Depression Scale (HADS)

    Time frame: Baseline (T0), 3 months (T1), 6 months (T2), and 12 months (T3)

    Change from baseline in HADS total score and subscales (anxiety and depression) in CBT + OPT vs OPT alone. The HADS consists of 14 items divided into two subscales (anxiety and depression, 7 items each); each subscale ranges from 0 to 21, with higher scores indicating greater psychological distress. The total score ranges from 0 to 42.

  2. Perceived Stress - Perceived Stress Scale (PSS)

    Time frame: Baseline (T0), 3 months (T1), 6 months (T2), and 12 months (T3)

    Change from baseline in perceived stress levels in CBT + OPT vs OPT alone. The PSS-10 consists of 10 items; scores range from 0 to 40, with higher scores indicating greater perceived stress.

  3. Somatic Symptom Burden - Patient Health Questionnaire (PHQ-15)

    Time frame: Baseline (T0), 3 months (T1), 6 months (T2), and 12 months (T3)

    A 15-item measure of somatic symptom severity (range: 0-30). Higher scores indicate greater somatic symptom burden.

  4. Patient Global Impression of Change (PGIC)

    Time frame: Baseline (T0), 3 months (T1), 6 months (T2), and 12 months (T3)

    Patient-reported subjective perception of overall improvement at each follow-up time point. A 7-point Likert scale assessing the patient's overall perception of improvement (range: 1-7). Higher scores indicate greater perceived improvement.

  5. Visceral Anxiety - Visceral Sensitivity Index (VSI)

    Time frame: Baseline (T0), 3 months (T1), 6 months (T2), and 12 months (T3)

    A 15-item scale assessing gastrointestinal-specific anxiety (range: 0-75). Higher scores indicate greater anxiety and hypervigilance toward gastrointestinal sensations.

  6. Serum Interleukin-6 (IL-6)

    Time frame: Baseline (T0), 3 months (T1), 6 months (T2), and 12 months (T3)

    Change from baseline in serum IL-6 levels (pg/mL) in CBT + OPT vs. OPT alone, as a marker of systemic inflammation.

  7. Serum Interleukin-8 (IL-8)

    Time frame: Baseline (T0), 3 months (T1), 6 months (T2), 12 months (T3)

    Change from baseline in serum IL-8 levels (pg/mL) in CBT + OPT vs. OPT alone, as a marker of systemic inflammation.

  8. Serum Interleukin-10 (IL-10)

    Time frame: Baseline (T0), 3 months (T1), 6 months (T2), 12 months (T3)

    Change from baseline in serum IL-10 levels (pg/mL) in CBT + OPT vs. OPT alone, as a marker of anti-inflammatory response.

  9. Serum Tumor Necrosis Factor-alpha (TNF-α)

    Time frame: Baseline (T0), 3 months (T1), 6 months (T2), and 12 months (T3)

    Change from baseline in serum TNF-α levels (pg/mL) in CBT + OPT vs. OPT alone, as a marker of systemic inflammation.

  10. High-sensitivity C-Reactive Protein (hs-CRP)

    Time frame: Baseline (T0), 3 months (T1), 6 months (T2), and 12 months (T3)

    Change from baseline in serum hs-CRP levels (mg/L) in CBT + OPT vs. OPT alone, as a marker of systemic low-grade inflammation.

  11. Diurnal Salivary Cortisol Profile

    Time frame: Baseline (T0), 3 months (T1), 6 months (T2), 12 months (T3)

    Change from baseline in diurnal salivary cortisol levels (nmol/L), measured at 4 time points across the day, in CBT + OPT vs. OPT alone, as a marker of hypothalamic-pituitary-adrenal (HPA) axis activity and stress regulation.

  12. Plasma Ghrelin

    Time frame: Baseline (T0), 3 months (T1), 6 months (T2), 12 months (T3)

    Change from baseline in plasma ghrelin levels (pg/mL) in CBT + OPT vs. OPT alone, as a marker of appetite regulation and gut-brain axis signaling.

  13. Plasma Cholecystokinin (CCK)

    Time frame: Baseline (T0), 3 months (T1), 6 months (T2), 12 months (T3)

    Change from baseline in plasma CCK levels (pg/mL) in CBT + OPT vs. OPT alone, as a marker of postprandial satiety signaling and gastrointestinal motility.

  14. Plasma Glucagon-Like Peptide-2 (GLP-2)

    Time frame: Baseline (T0), 3 months (T1), 6 months (T2), 12 months (T3)

    Change from baseline in plasma GLP-2 levels (pg/mL) in CBT + OPT vs. OPT alone, as a marker of intestinal barrier integrity and mucosal growth.

  15. Plasma Peptide YY (PYY)

    Time frame: Baseline (T0), 3 months (T1), 6 months (T2), 12 months (T3)

    Change from baseline in plasma PYY levels (pg/mL) in CBT + OPT vs. OPT alone, as a marker of postprandial satiety and gut motility regulation.

  16. Plasma Gastrin

    Time frame: Baseline (T0), 3 months (T1), 6 months (T2), 12 months (T3)

    Change from baseline in plasma gastrin levels (pg/mL) in CBT + OPT vs. OPT alone, as a marker of gastric acid secretion and mucosal function.

  17. Plasma Motilin

    Time frame: Baseline (T0), 3 months (T1), 6 months (T2), 12 months (T3)

    Change from baseline in plasma motilin levels (pg/mL) in CBT + OPT vs. OPT alone, as a marker of gastric motility and interdigestive motor activity.

  18. Plasma Leptin

    Time frame: Baseline (T0), 3 months (T1), 6 months (T2), 12 months (T3)

    Change from baseline in plasma leptin levels (ng/mL) in CBT + OPT vs. OPT alone, as a marker of energy homeostasis and neuroendocrine regulation.

  19. Plasma Serotonin (5-HT)

    Time frame: Baseline (T0), 3 months (T1), 6 months (T2), 12 months (T3)

    Change from baseline in plasma serotonin levels (ng/mL) in CBT + OPT vs. OPT alone, as a marker of enteric nervous system signaling and gut-brain communication.

  20. Plasma Brain-Derived Neurotrophic Factor (BDNF)

    Time frame: Baseline (T0), 3 months (T1), 6 months (T2), 12 months (T3)

    Change from baseline in plasma BDNF levels (pg/mL) in CBT + OPT vs. OPT alone, as a marker of neuroplasticity and gut-brain axis modulation.

  21. Plasma Cortisol

    Time frame: Baseline (T0), 3 months (T1), 6 months (T2), 12 months (T3)

    Change from baseline in plasma cortisol levels (nmol/L) in CBT + OPT vs. OPT alone, as a marker of hypothalamic-pituitary-adrenal (HPA) axis activation and physiological stress response.

  22. Fecal Zonulin

    Time frame: Baseline (T0), 3 months (T1), 6 months (T2), and 12 months (T3)

    Change from baseline in fecal zonulin levels (ng/mL) in CBT + OPT vs. OPT alone, as a marker of intestinal barrier permeability and tight junction regulation.

  23. Fecal Calprotectin

    Time frame: Baseline (T0), 3 months (T1), 6 months (T2), 12 months (T3)

    Change from baseline in fecal calprotectin levels (µg/g) in CBT + OPT vs. OPT alone, as a marker of intestinal mucosal inflammation.

  24. Gut Microbiota Alpha Diversity - Observed Species

    Time frame: Baseline (T0), 3 months (T1), 6 months (T2), and 12 months (T3)

    Change from baseline in observed species richness (count). Higher values indicate greater microbial richness.

  25. Gut Microbiota Beta Diversity - UniFrac Distance

    Time frame: Baseline (T0), 3 months (T1), 6 months (T2), 12 months (T3)

    Change from baseline in UniFrac distance (unitless), reflecting phylogenetic dissimilarity between microbial communities. Higher values indicate greater dissimilarity.

  26. Gut Microbiota Beta Diversity - Bray-Curtis Dissimilarity

    Time frame: Baseline (T0), 3 months (T1 - end of intervention), 6 months (T2 - intermediate follow-up), 12 months (T3 - final follow-up)

    Change from baseline in Bray-Curtis dissimilarity index (unitless). Higher values indicate greater compositional differences.

  27. Relative Abundance of Faecalibacterium prausnitzii

    Time frame: Baseline (T0), 3 months (T1), 6 months (T2), 12 months (T3)

    Change from baseline in relative abundance (%) assessed by 16S rRNA sequencing in CBT + OPT vs. OPT alone.

  28. Relative Abundance of Bifidobacterium spp.

    Time frame: Baseline (T0), 3 months (T1), 6 months (T2), 12 months (T3)

    Change from baseline in relative abundance (%) assessed by 16S rRNA sequencing.

  29. Predicted Butyrate Production Pathway Abundance

    Time frame: Baseline (T0), 3 months (T1), 6 months (T2), 12 months (T3)

    Change from baseline in predicted abundance (arbitrary units) derived from 16S rRNA data in CBT + OPT vs. OPT alone.

  30. Fecal Acetate

    Time frame: Baseline (T0), 3 months (T1), 6 months (T2), and 12 months (T3)

    Change from baseline in fecal acetate concentration (µmol/g) in CBT + OPT vs. OPT alone

  31. Fecal Propionate

    Time frame: Baseline (T0), 3 months (T1), 6 months (T2), and 12 months (T3)

    Change from baseline in fecal propionate concentration (µmol/g).

  32. Fecal Butyrate

    Time frame: Baseline (T0), 3 months (T1), 6 months (T2), and 12 months (T3)

    Change from baseline in fecal butyrate concentration (µmol/g).

Other outcomes

  1. Weekly Symptom Diary - Frequency and Intensity of Gastrointestinal Symptoms

    Time frame: Weekly from baseline through 12 months (T3)

    Self-reported daily frequency and intensity of gastrointestinal symptoms and medication use, recorded in a structured weekly diary throughout the study period using a numeric rating scale (range: 0-10). Higher scores indicate greater symptom severity.

  2. CBT Adherence Rate

    Time frame: 3 months (T1) and 6 months (T2 - booster session)

    Proportion of participants who complete the planned cognitive behavioral therapy (CBT) sessions (10 individual sessions and a booster session at 6 months), expressed as a percentage. Higher values indicate greater adherence to the intervention.

  3. CBT Drop-out Rate

    Time frame: 3 months (T1) and 6 months (T2 - booster session)

    Proportion of participants who discontinue the CBT intervention before completion, expressed as a percentage (%). Higher values indicate lower acceptability of the intervention.

  4. Medication Use - Consumption of PPIs, Antacids, and Prokinetics

    Time frame: Baseline (T0), 3 months (T1), 6 months (T2), 12 months (T3)

    Change from baseline in the use of pharmacological treatments (proton pump inhibitors, antacids, prokinetics) as a proxy measure of clinical improvement and healthcare resource utilization.

  5. Automatic Thoughts and Cognitive Triggers (CBT group only)

    Time frame: Throughout the intervention (Months 3-6) and at 6 months (T2)

    Exploratory analysis of CBT-specific cognitive variables, including automatic thoughts and behavioral triggers recorded on structured CBT sheets, as potential mediators of symptom improvement in the CBT + OPT group.

  6. Per-Protocol Subgroup Analysis

    Time frame: 12 months (T3)

    Pre-specified per-protocol analysis was restricted to participants who completed at least 80% of the CBT sessions and all biological sampling time points to assess treatment efficacy under optimal adherence conditions.

Study contacts

Contact information is provided by the study sponsor or research team.

Francesco Russo, MD

CONTACT

[email protected]

+390804994129

Laura Prospero, Psychologist

CONTACT

[email protected]

+390804994274

Sponsors and collaborators

Lead sponsor

Azienda Ospedaliera Specializzata in Gastroenterologia Saverio de Bellis

Other

Registry information

Official study title

Multimodal Phenotyping of Functional Dyspepsia: Controlled Trial on Response to Cognitive-Behavioral Therapy in Subtypes of Epigastric Pain Syndrome and Postprandial Discomfort Syndrome

Acronym: FD-CBT

Important dates

Study start
2026
Primary completion
2027
Study completion
2028
First posted
May 11, 2026
Registry last updated
May 11, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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