An interventional study of Optimized Standard Treatment (OPT) and Cognitive Behavioral Therapy + Optimized Standard Treatment (CBT + OPT) in Functional Dyspepsia, Epigastric Pain Syndrome and Postprandial Distress Syndrome, sponsored by Azienda Ospedaliera Specializzata in Gastroenterologia Saverio de Bellis. Not yet recruiting. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2026-05-11.
Sponsored by Azienda Ospedaliera Specializzata in Gastroenterologia Saverio de Bellis · Not applicable, Interventional, and Treatment
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
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.
3,536 studies on the registry are indexed under Inflammation; 642 are open to participants now.
This study's planned enrollment of 90 is above the median of 50 across 2,577 interventional studies indexed under Inflammation.
Browse Inflammation studies →Azienda Ospedaliera Specializzata in Gastroenterologia Saverio de Bellis is the lead sponsor of 55 studies on the registry; 19 are open to participants now.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants receive standard medical treatment for Functional Dyspepsia, including proton pump inhibitors, antiacids, and prokinetics at standard doses, according to clinical guidelines. No additional psychological intervention is provided.
Drug: Optimized Standard Treatment (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 include psychoeducation, cognitive restructuring, stress management, coping strategies, interoceptive and behavioral exposure, relaxation, and nutritional integration. Adherence and engagement are monitored throughout the study.
Drug: Optimized Standard Treatment (OPT) · Behavioral: Cognitive Behavioral Therapy + Optimized Standard Treatment (CBT + 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.
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.
Reduction in gastrointestinal symptom severity as assessed by the Leeds Dyspepsia Questionnaire - Short Form (LDQ-SF)
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.
Time frame: Baseline (T0), 3 months (T1 - end of intervention), 6 months (T2 - intermediate follow-up), 12 months (T3 - final follow-up)
Anxiety and Depression - Hospital Anxiety and Depression Scale (HADS)
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.
Time frame: Baseline (T0), 3 months (T1), 6 months (T2), and 12 months (T3)
Perceived Stress - Perceived Stress Scale (PSS)
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.
Time frame: Baseline (T0), 3 months (T1), 6 months (T2), and 12 months (T3)
Somatic Symptom Burden - Patient Health Questionnaire (PHQ-15)
A 15-item measure of somatic symptom severity (range: 0-30). Higher scores indicate greater somatic symptom burden.
Time frame: Baseline (T0), 3 months (T1), 6 months (T2), and 12 months (T3)
Patient Global Impression of Change (PGIC)
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.
Time frame: Baseline (T0), 3 months (T1), 6 months (T2), and 12 months (T3)
Visceral Anxiety - Visceral Sensitivity Index (VSI)
A 15-item scale assessing gastrointestinal-specific anxiety (range: 0-75). Higher scores indicate greater anxiety and hypervigilance toward gastrointestinal sensations.
Time frame: Baseline (T0), 3 months (T1), 6 months (T2), and 12 months (T3)
Serum Interleukin-6 (IL-6)
Change from baseline in serum IL-6 levels (pg/mL) in CBT + OPT vs. OPT alone, as a marker of systemic inflammation.
Time frame: Baseline (T0), 3 months (T1), 6 months (T2), and 12 months (T3)
Serum Interleukin-8 (IL-8)
Change from baseline in serum IL-8 levels (pg/mL) in CBT + OPT vs. OPT alone, as a marker of systemic inflammation.
Time frame: Baseline (T0), 3 months (T1), 6 months (T2), 12 months (T3)
Serum Interleukin-10 (IL-10)
Change from baseline in serum IL-10 levels (pg/mL) in CBT + OPT vs. OPT alone, as a marker of anti-inflammatory response.
Time frame: Baseline (T0), 3 months (T1), 6 months (T2), 12 months (T3)
Serum Tumor Necrosis Factor-alpha (TNF-α)
Change from baseline in serum TNF-α levels (pg/mL) in CBT + OPT vs. OPT alone, as a marker of systemic inflammation.
Time frame: Baseline (T0), 3 months (T1), 6 months (T2), and 12 months (T3)
High-sensitivity C-Reactive Protein (hs-CRP)
Change from baseline in serum hs-CRP levels (mg/L) in CBT + OPT vs. OPT alone, as a marker of systemic low-grade inflammation.
Time frame: Baseline (T0), 3 months (T1), 6 months (T2), and 12 months (T3)
Diurnal Salivary Cortisol Profile
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.
Time frame: Baseline (T0), 3 months (T1), 6 months (T2), 12 months (T3)
Plasma Ghrelin
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.
Time frame: Baseline (T0), 3 months (T1), 6 months (T2), 12 months (T3)
Plasma Cholecystokinin (CCK)
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.
Time frame: Baseline (T0), 3 months (T1), 6 months (T2), 12 months (T3)
Plasma Glucagon-Like Peptide-2 (GLP-2)
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.
Time frame: Baseline (T0), 3 months (T1), 6 months (T2), 12 months (T3)
Plasma Peptide YY (PYY)
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.
Time frame: Baseline (T0), 3 months (T1), 6 months (T2), 12 months (T3)
Plasma Gastrin
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.
Time frame: Baseline (T0), 3 months (T1), 6 months (T2), 12 months (T3)
Plasma Motilin
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.
Time frame: Baseline (T0), 3 months (T1), 6 months (T2), 12 months (T3)
Plasma Leptin
Change from baseline in plasma leptin levels (ng/mL) in CBT + OPT vs. OPT alone, as a marker of energy homeostasis and neuroendocrine regulation.
Time frame: Baseline (T0), 3 months (T1), 6 months (T2), 12 months (T3)
Plasma Serotonin (5-HT)
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.
Time frame: Baseline (T0), 3 months (T1), 6 months (T2), 12 months (T3)
Plasma Brain-Derived Neurotrophic Factor (BDNF)
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.
Time frame: Baseline (T0), 3 months (T1), 6 months (T2), 12 months (T3)
Plasma Cortisol
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.
Time frame: Baseline (T0), 3 months (T1), 6 months (T2), 12 months (T3)
Fecal Zonulin
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.
Time frame: Baseline (T0), 3 months (T1), 6 months (T2), and 12 months (T3)
Fecal Calprotectin
Change from baseline in fecal calprotectin levels (µg/g) in CBT + OPT vs. OPT alone, as a marker of intestinal mucosal inflammation.
Time frame: Baseline (T0), 3 months (T1), 6 months (T2), 12 months (T3)
Gut Microbiota Alpha Diversity - Observed Species
Change from baseline in observed species richness (count). Higher values indicate greater microbial richness.
Time frame: Baseline (T0), 3 months (T1), 6 months (T2), and 12 months (T3)
Gut Microbiota Beta Diversity - UniFrac Distance
Change from baseline in UniFrac distance (unitless), reflecting phylogenetic dissimilarity between microbial communities. Higher values indicate greater dissimilarity.
Time frame: Baseline (T0), 3 months (T1), 6 months (T2), 12 months (T3)
Gut Microbiota Beta Diversity - Bray-Curtis Dissimilarity
Change from baseline in Bray-Curtis dissimilarity index (unitless). Higher values indicate greater compositional differences.
Time frame: Baseline (T0), 3 months (T1 - end of intervention), 6 months (T2 - intermediate follow-up), 12 months (T3 - final follow-up)
Relative Abundance of Faecalibacterium prausnitzii
Change from baseline in relative abundance (%) assessed by 16S rRNA sequencing in CBT + OPT vs. OPT alone.
Time frame: Baseline (T0), 3 months (T1), 6 months (T2), 12 months (T3)
Relative Abundance of Bifidobacterium spp.
Change from baseline in relative abundance (%) assessed by 16S rRNA sequencing.
Time frame: Baseline (T0), 3 months (T1), 6 months (T2), 12 months (T3)
Predicted Butyrate Production Pathway Abundance
Change from baseline in predicted abundance (arbitrary units) derived from 16S rRNA data in CBT + OPT vs. OPT alone.
Time frame: Baseline (T0), 3 months (T1), 6 months (T2), 12 months (T3)
Fecal Acetate
Change from baseline in fecal acetate concentration (µmol/g) in CBT + OPT vs. OPT alone
Time frame: Baseline (T0), 3 months (T1), 6 months (T2), and 12 months (T3)
Fecal Propionate
Change from baseline in fecal propionate concentration (µmol/g).
Time frame: Baseline (T0), 3 months (T1), 6 months (T2), and 12 months (T3)
Fecal Butyrate
Change from baseline in fecal butyrate concentration (µmol/g).
Time frame: Baseline (T0), 3 months (T1), 6 months (T2), and 12 months (T3)
Weekly Symptom Diary - Frequency and Intensity of Gastrointestinal Symptoms
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.
Time frame: Weekly from baseline through 12 months (T3)
CBT Adherence Rate
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.
Time frame: 3 months (T1) and 6 months (T2 - booster session)
CBT Drop-out Rate
Proportion of participants who discontinue the CBT intervention before completion, expressed as a percentage (%). Higher values indicate lower acceptability of the intervention.
Time frame: 3 months (T1) and 6 months (T2 - booster session)
Medication Use - Consumption of PPIs, Antacids, and Prokinetics
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.
Time frame: Baseline (T0), 3 months (T1), 6 months (T2), 12 months (T3)
Automatic Thoughts and Cognitive Triggers (CBT group only)
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.
Time frame: Throughout the intervention (Months 3-6) and at 6 months (T2)
Per-Protocol Subgroup Analysis
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.
Time frame: 12 months (T3)
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Azienda Ospedaliera Specializzata in Gastroenterologia Saverio de Bellis