E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Achalasia is a motility disorder of the esophagus. Disappearance of myenteric neurons in the esophageal wall leads to failure of relaxation of the lower esophageal sphincter (LES) and impaired peristalsis. Symptoms of achalasia include dysphagia, regurgitation, chest pain and weight loss due to the stasis of food and liquids in the esophagus. Treatments effectively diminish the symptoms dysphagia and regurgitation, however have little effect on the occurrence of chest pain. |
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E.1.1.1 | Medical condition in easily understood language |
Achalasia is a motility disorder of the esophagus. Symptoms of achalasia include dysphagia, regurgitation, chest pain and weight loss due to the stasis of food and liquids in the esophagus. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Symptoms and general pathology [C23] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To investigate the effect of citalopram, as compared to a placebo, on spontaneous chest pain episodes in patients with achalasia. |
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E.2.2 | Secondary objectives of the trial |
Secondary Objectives: • To compare chest pain frequency, intensity and duration after treatment with citalopram or placebo. • To evaluate the effect of treatment with citalopram or placebo on the health status, psychological state and anxiety of the patient. • To assess the side-effects of the treatment with citalopram.
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
The pathophysiology of chronic chest pain achalasia patients is still unknown. To further elucidate this mechanism and the effect of citalopram on esophageal sensitivity, an acid perfusion and barostat balloon distention test will be performed in a subgroup of patients. At the start of the study, patient will be asked to participate in this subgroup analysis. If they are willing to participate, these two additional tests will be performed.
Objectives sub-study: • To investigate the effect of citalopram, as compared to placebo, on esophageal sensitivity to acid infusion and balloon distension in achalasia patients with chest pain. • To compare esophageal sensitivity to acid infusion and distension in achalasia patients with and without chest pain and in healthy controls.
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E.3 | Principal inclusion criteria |
• Written informed consent • Minimum age: 18 years • Diagnosed with achalasia type 1 or 2, confirmed by high-resolution manometry • Previously treated with pneumodilatation, Heller’s myotomy or POEM • ≥3 months post-treatment for achalasia • Recurrent chest pain o Midline chest pain or discomfort that is not of burning quality o At least 3 episodes per week of unexplained chest pain, for a minimum of 3 months. o No significant stasis, defined as <2cm stasis after 5 minutes on timed barium esophagram o At start of symptoms, no sign of reflux esophagitis on last esophagogastroduodenoscopy
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E.4 | Principal exclusion criteria |
• Achalasia type 3 (‘’spastic type’’) or spastic contractions on high-resolution manometry • Surgery of the esophagus except Heller’s myotomy and POEM • Currently using antidepressants • Chest pain suspect of cardiac origin. • Severe and clinically unstable concomitant disease (e.g. liver, cardiovascular or lung disease, neurological or psychiatric disorders, cancer or AIDS and other endocrine disorders) • Pregnancy or lactation. A pregnancy test will be carried out prior to inclusion in the study. Female patients who are premenopausal and have a negative pregnancy test should be on an anticonceptive. • Medication-related: Allergy to barium sulfate or contra-indications for citalopram use
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E.5 End points |
E.5.1 | Primary end point(s) |
Global assessment of chest pain after 6 weeks of treatment with citalopram. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• Symptom frequency and symptom severity score (calculated from symptom diary) • Health-related Quality of life (SF-36) • Achalasia-specific health-related quality of life (Ach-HRQL) • Hospital Anxiety and depression scale (HADS) • Symptom severity and time to perception during esophageal acid perfusion and during esophageal barostat balloon distension test (sub-study). • Adverse events/ complications/ side-effects
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The symptoms will be assessed daily using a symptom diary. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of the trial will be at the end follow up of the last patient included. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |