Epigastric Pain Syndrome, Functional Dyspepsia, Postprandial Distress Syndrome
Conditions
Keywords
Functional Dyspepsia, Cognitive Behavioral Therapy, Epigastric Pain Syndrome, Postprandial Distress Syndrome, Gut-Brain Axis, Microbiota, Randomized Controlled Trial, Disorders of Gut-Brain Interaction, Gastrointestinal Symptoms, Inflammation, Biomarkers, Precision Medicine
Brief summary
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
Detailed description
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.
Interventions
DRUGOptimized Standard Treatment (OPT)
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.
BEHAVIORALCognitive Behavioral Therapy + Optimized Standard Treatment (CBT + OPT)
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.
Sponsors
Azienda Ospedaliera Specializzata in Gastroenterologia Saverio de Bellis
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Reduction in gastrointestinal symptom severity as assessed by the Leeds Dyspepsia Questionnaire - Short Form (LDQ-SF) | 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
| Measure | Time frame | Description |
|---|---|---|
| Gut Microbiota Alpha Diversity - Observed Species | 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. |
| Gut Microbiota Beta Diversity - UniFrac Distance | 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. |
| Gut Microbiota Beta Diversity - Bray-Curtis Dissimilarity | 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. |
| Relative Abundance of Faecalibacterium prausnitzii | 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. |
| Relative Abundance of Bifidobacterium spp. | Baseline (T0), 3 months (T1), 6 months (T2), 12 months (T3) | Change from baseline in relative abundance (%) assessed by 16S rRNA sequencing. |
| Predicted Butyrate Production Pathway Abundance | 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. |
| Fecal Acetate | 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 |
| Fecal Propionate | Baseline (T0), 3 months (T1), 6 months (T2), and 12 months (T3) | Change from baseline in fecal propionate concentration (µmol/g). |
| Fecal Butyrate | Baseline (T0), 3 months (T1), 6 months (T2), and 12 months (T3) | Change from baseline in fecal butyrate concentration (µmol/g). |
| Anxiety and Depression - Hospital Anxiety and Depression Scale (HADS) | 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. |
| Perceived Stress - Perceived Stress Scale (PSS) | 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. |
| Somatic Symptom Burden - Patient Health Questionnaire (PHQ-15) | 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. |
| Patient Global Impression of Change (PGIC) | 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. |
| Visceral Anxiety - Visceral Sensitivity Index (VSI) | 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. |
| Serum Interleukin-6 (IL-6) | 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. |
| Serum Interleukin-8 (IL-8) | 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. |
| Serum Interleukin-10 (IL-10) | 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. |
| Serum Tumor Necrosis Factor-alpha (TNF-α) | 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. |
| High-sensitivity C-Reactive Protein (hs-CRP) | 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. |
| Diurnal Salivary Cortisol Profile | 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. |
| Plasma Ghrelin | 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. |
| Plasma Cholecystokinin (CCK) | 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. |
| Plasma Glucagon-Like Peptide-2 (GLP-2) | 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. |
| Plasma Peptide YY (PYY) | 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. |
| Plasma Gastrin | 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. |
| Plasma Motilin | 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. |
| Plasma Leptin | 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. |
| Plasma Serotonin (5-HT) | 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. |
| Plasma Brain-Derived Neurotrophic Factor (BDNF) | 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. |
| Plasma Cortisol | 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. |
| Fecal Calprotectin | 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. |
| Fecal Zonulin | 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. |
Contacts
CONTACTLaura Prospero, Psychologist
CONTACTFrancesco Russo, MD
Outcome results
None listed