Idiopathic Gastroparesis
Conditions
Keywords
idiopathic gastroparesis
Brief summary
The principal objective of this multicenter, randomized, placebo-controlled trial is to evaluate whether treatment with nortriptyline will improve gastroparesis symptoms compared with placebo.
Interventions
Nortriptyline; 10 mg, one capsule, po qhs (by mouth at bedtime each night) x 3 weeks, f03 visit, 25 mg, one capsule, po qhs x 3 weeks, f06 visit, 50 mg, two capsules, po qhs x 3 weeks, f09 visit, 75 mg, three capsules, po qhs x 6 weeks, f15 visit: taper study drug by one capsule a week, off study drug for the last week
DRUGPlacebo (for nortriptyline)
Placebo (for nortriptyline), 10 mg, one capsule, po qhs x 3 weeks, f03 visit, 25 mg, one capsule, po qhs x 3 weeks;
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
21 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Age 21 through 65 years old at registration * Documentation of delayed gastric emptying on gastric emptying scintigraphy within 2 years of registration, defined as greater than 60% retention at 2 hours or greater than 10% retention at 4 hours * Symptoms of gastroparesis for at least 6 months (does not have to be contiguous) prior to registration with Gastroparesis Cardinal Symptom Index (GCSI) score of 21 or greater * Negative upper endoscopy or upper GI series within 2 years of registration
Exclusion criteria
* Normal gastric emptying confirmed with scintigraphy * Diabetic gastroparesis or post-surgical gastroparesis including fundoplication * Another active disorder which could explain symptoms in the opinion of the investigator * History of significant cardiac arrhythmias and/or prolonged QTc * History of seizures * Use of narcotics more than 3 days per week * Use of tricyclic antidepressants for refractory symptoms of gastroparesis within 6 weeks prior to randomization * Use of strongly anticholinergic medications * Use of calcium channel blockers * Use of erythromycin * Clear history of failed trial of nortriptyline use for gastroparetic symptoms * Symptoms of primary depression or suicidal ideation * Contraindications to nortriptyline: 1. hypersensitivity or allergy to any tricyclic antidepressant drug 2. concomitant therapy with a monoamine oxidase inhibitor (MAOI) 3. recent myocardial infarction 4. glaucoma * Pregnancy or nursing * Any other condition, which in the opinion of the investigator would impede compliance or hinder completion of the study * Use of a G tube, J tube,or a central catheter for nutrition * Use of a gastric electrical stimulator * Failure to give informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Decrease From the Baseline GCSI of at Least 50% on Any Two Consecutive Follow-up Visits | at end of treatment, 15 weeks from baseline assessment | A decrease from the baseline Gastroparesis Cardinal Symptom Index (GCSI) score (sum of the 9 individual symptom scores) of at least 50% on any two consecutive follow-up visits during the 15 week treatment period with maximum tolerated study drug dose. The total score ranges from 0-45 with higher scores indicating greater symptom severity. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Nortriptyline Nortriptyline Hydrochloride dose escalation from 10 mg to 75 mg
Nortriptyline Hydrochloride: Nortriptyline; 10 mg, one capsule, po qhs (by mouth at bedtime each night) x 3 weeks, f03 visit, 25 mg, one capsule, po qhs x 3 weeks, f06 visit, 50 mg, two capsules, po qhs x 3 weeks, f09 visit, 75 mg, three capsules, po qhs x 6 weeks, f15 visit: taper study drug by one capsule a week, off study drug for the last week | 65 |
| Placebo No treatment
Nortriptyline-Placebo: Nortriptyline-placebo, 10 mg, one capsule, po qhs x 3 weeks, f03 visit, 25 mg, one capsule, po qhs x 3 weeks; f06 visit, 50 mg, two capsules, po qhs x 3 weeks; f09 visit, 75 mg, three capsules, po qhs x 6 weeks, po qhs x 15 wks f15 visit: taper study drug by one capsule a week, off study drug for the last week | 65 |
| Total | 130 |
Baseline characteristics
| Characteristic | Nortriptyline | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 42 years STANDARD_DEVIATION 12 | 40 years STANDARD_DEVIATION 12 | 41 years STANDARD_DEVIATION 12 |
| antiemetics taken in last month | 39 participants | 33 participants | 72 participants |
| Beck Depression Inventory- severe depression score | 12 participants | 15 participants | 27 participants |
| Beck Depression Inventory- total score | 17 units on a scale STANDARD_DEVIATION 11 | 18 units on a scale STANDARD_DEVIATION 12 | 17 units on a scale STANDARD_DEVIATION 12 |
| benzodiazepine taken in last month | 26 participants | 14 participants | 40 participants |
| Body mass index | 27 kg/m^2 STANDARD_DEVIATION 5 | 28 kg/m^2 STANDARD_DEVIATION 7 | 27 kg/m^2 STANDARD_DEVIATION 6 |
| Brief Pain Inventory- interference score | 4.2 units on a scale STANDARD_DEVIATION 3 | 4.1 units on a scale STANDARD_DEVIATION 3.3 | 4.1 units on a scale STANDARD_DEVIATION 3.1 |
| Brief Pain Inventory- severity score | 4.0 units on a scale STANDARD_DEVIATION 2.5 | 4.1 units on a scale STANDARD_DEVIATION 2.7 | 4.0 units on a scale STANDARD_DEVIATION 2.6 |
| clinical global patient impression score | -0.7 units on a scale STANDARD_DEVIATION 0.9 | -0.7 units on a scale STANDARD_DEVIATION 1.2 | -0.7 units on a scale STANDARD_DEVIATION 1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants | 8 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 58 Participants | 57 Participants | 115 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Gastroparesis Symptom Rating Scale score | 3.6 units on a scale STANDARD_DEVIATION 1.1 | 3.7 units on a scale STANDARD_DEVIATION 1.2 | 3.6 units on a scale STANDARD_DEVIATION 1.2 |
| GI symptom diarrhea sub score | 1.8 units on a scale STANDARD_DEVIATION 1.7 | 2.0 units on a scale STANDARD_DEVIATION 1.8 | 1.9 units on a scale STANDARD_DEVIATION 1.8 |
| GI symptoms constipation sub score | 2.8 units on a scale STANDARD_DEVIATION 1.9 | 2.4 units on a scale STANDARD_DEVIATION 1.7 | 2.6 units on a scale STANDARD_DEVIATION 1.8 |
| GSCI- bloating sub score | 7.2 units on a scale STANDARD_DEVIATION 2.9 | 7.0 units on a scale STANDARD_DEVIATION 2.7 | 7.1 units on a scale STANDARD_DEVIATION 2.8 |
| GSCI- nausea sub score | 8.2 units on a scale STANDARD_DEVIATION 3.6 | 8.2 units on a scale STANDARD_DEVIATION 4.2 | 8.2 units on a scale STANDARD_DEVIATION 3.9 |
| GSCI- satiety sub score | 15.4 units on a scale STANDARD_DEVIATION 3.4 | 15.1 units on a scale STANDARD_DEVIATION 4.1 | 15.3 units on a scale STANDARD_DEVIATION 3.7 |
| GSCI total score | 30.9 units on a scale STANDARD_DEVIATION 6.1 | 30.3 units on a scale STANDARD_DEVIATION 6.5 | 30.6 units on a scale STANDARD_DEVIATION 6.3 |
| PAGI-SYM- GERD sub score | 15.4 units on a scale STANDARD_DEVIATION 9.4 | 17.9 units on a scale STANDARD_DEVIATION 10.5 | 16.7 units on a scale STANDARD_DEVIATION 10.7 |
| PAGI-SYM- lower abdominal pain sub score | 4.7 units on a scale STANDARD_DEVIATION 3.3 | 4.3 units on a scale STANDARD_DEVIATION 3.3 | 4.5 units on a scale STANDARD_DEVIATION 3.3 |
| PAGI-SYM nausea/vomiting predominant symptom | 27 participants | 22 participants | 49 participants |
| PAGI-SYM- upper abdominal pain sub score | 6.8 units on a scale STANDARD_DEVIATION 2.9 | 6.5 units on a scale STANDARD_DEVIATION 2.9 | 6.6 units on a scale STANDARD_DEVIATION 2.9 |
| Patient Health Questionnaire-15 | 14 units on a scale STANDARD_DEVIATION 5 | 14 units on a scale STANDARD_DEVIATION 5 | 14 units on a scale STANDARD_DEVIATION 5 |
| prokinetic taken in last month | 23 participants | 25 participants | 48 participants |
| proton-pump inhibitor taken in last month | 48 participants | 49 participants | 97 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 10 Participants | 9 Participants | 19 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 54 Participants | 54 Participants | 108 Participants |
| Region of Enrollment United States | 65 participants | 65 participants | 130 participants |
| selective serotonin reuptake inhibitor taken in last month | 7 participants | 11 participants | 18 participants |
| Sex: Female, Male Female | 60 Participants | 56 Participants | 116 Participants |
| Sex: Female, Male Male | 5 Participants | 9 Participants | 14 Participants |
| SF-36 Quality of Life -Mental component | 41 units on a scale STANDARD_DEVIATION 13 | 40 units on a scale STANDARD_DEVIATION 13 | 40 units on a scale STANDARD_DEVIATION 13 |
| SF-36 Quality of Life - Physical component | 35 units on a scale STANDARD_DEVIATION 10 | 36 units on a scale STANDARD_DEVIATION 10 | 35 units on a scale STANDARD_DEVIATION 10 |
| State Trait Anxiety Inventory- State Anxiety score | 42 units on a scale STANDARD_DEVIATION 13 | 41 units on a scale STANDARD_DEVIATION 12 | 42 units on a scale STANDARD_DEVIATION 12 |
| State Trait Anxiety Inventory- Trait Anxiety score | 43 units on a scale STANDARD_DEVIATION 12 | 43 units on a scale STANDARD_DEVIATION 13 | 43 units on a scale STANDARD_DEVIATION 12 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 18 / 65 | 23 / 65 |
| serious Total, serious adverse events | 5 / 65 | 1 / 65 |
Outcome results
Primary
Decrease From the Baseline GCSI of at Least 50% on Any Two Consecutive Follow-up Visits
A decrease from the baseline Gastroparesis Cardinal Symptom Index (GCSI) score (sum of the 9 individual symptom scores) of at least 50% on any two consecutive follow-up visits during the 15 week treatment period with maximum tolerated study drug dose. The total score ranges from 0-45 with higher scores indicating greater symptom severity.
Time frame: at end of treatment, 15 weeks from baseline assessment
Population: intention to treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nortriptyline | Decrease From the Baseline GCSI of at Least 50% on Any Two Consecutive Follow-up Visits | 15 participants |
| Placebo | Decrease From the Baseline GCSI of at Least 50% on Any Two Consecutive Follow-up Visits | 14 participants |
p-value: 0.86Mantel Haenszel