Objectives of the study:

Primary:

To determine the efficacy of Mirtazapine compared to Amitriptyline as add-on treatment to standard-of-care for FDIGE in decreasing dyspepsia symptom score

Secondary:

1.       To evaluate efficacy of Mirtazapine compared to Amitriptyline as add-on treatment to standard-of-care for FDIGE in improving gastric emptying as assessed by GES

2.       To compare proportion of patients achieving at least 50% reduction in symptom score within 4 and 8 weeks of treatment in each treatment arm

3.       To assess the adverse effects of drugs in both treatment arms 

Study design

Randomized; Open-label; Active-controlled; Two-treatment, two-period cross-over; Academic clinical trial

Study site

Department of Gastroenterology OPD and Department of Pharmacology

Methods (e.g. PICO)

Population :–

Inclusion criteria:

Patients with-

·       FD (ROME-IV criteria) with impaired gastric motility (GES- retained meal value>60% at 2 hrs or >10% at 4 hrs-delayed emptying-Abell et al,2008)

·        no overt anxiety/depression (subscale of HADS–HAS/HDS scores<7)

·        Age 18-60 yrs

·        Voluntary consent

·        No evidence of structural disease explaining dyspeptic symptoms

Exclusion criteria:

Patients with-

·        Diabetes mellitus

·        Organic brain syndrome

·        Moderate/Severe Depression

·        History of psychosis, bipolar disorder, substance abuse/dependence

·        Any psychotropic medication

·        Suicidal ideation in past 2wks (by PHQ)

·        GERD

·        Concurrent medications affecting GI motility

·        History of gastric surgery

Sample size 

To achieve a power of 80% and a level of significance (Type-1 error) of 5% (two sided), assuming a pooled standard deviation of NDIS score of 3.5, the study would require a sample size of 40 for each group, to detect a mean difference of NDIS score of 2.22 (based on Jamshidfar N, et al. 2023). 

Assuming 20% attrition rate, a total of 100 patients is needed for the study (50 for each arm).

Intervention â€“ 

Mirtazapine 7.5 mg/day at bedtime for 2 wks; then 15 mg/day for 10 wks (total-12 wks)

Comparator–Amitriptyline 10 mg/day at bedtime for 2 wks; then 25 mg/day for 10 wks (total-12 wks)

Outcomes â€“ 

1. Change in scores of sNDIS scale from baseline

2. Outcomes–improvement in gastric emptying as assessed by GES

3. Outcomes–proportion of patients with at least 50%reduction in symptom score within 4 and 8 wks 

 Statistical analysis 

Data would be analyzed by mITT method (Data of at least one physical follow-up at 4 weeks of treatment would be carried forward)

Distribution pattern of data would be determined by Q-Q plot/Shapiro-Wilk test 

If data distribution is not Gaussian, Fischer Exact/Chi-square test would be used for proportions of patients achieving at least 50% reduction in score 

Kruskal Wallis Test would be used for comparing improvement of scores from baseline 

Friedman’s ANOVA would be used for comparing difference of sNDIS score among the treatment groups