Gastroparesis, a syndrome in which patients experience delayed gastric emptying, is characterized by symptoms such as nausea, vomiting, bloating, abdominal pain, and early satiety. Management of gastroparesis is limited by few effective treatments, many of which function by accelerating gastric emptying. Based on the hypothesis that some symptoms of gastroparesis arise because of neuropathic changes in enteric and sensory nerves, tricyclic antidepressants (TCAs) in low doses have been used as neuromodulators to treat refractory symptoms of nausea, vomiting, and abdominal pain, but there is little evidence to support this use. The Nortriptyline for Idiopathic Gastroparesis (NORIG) study is a multicenter, randomized, clinical trial that was designed by the Gastroparesis Clinical Research Consortium (GpCRC) to test whether treatment with nortriptyline, a TCA with reduced anticholinergic side effects, results in symptomatic improvement in patients with idiopathic gastroparesis.
Individuals between the ages of 21 and 68 years old with moderate to severe symptoms of idiopathic gastroparesis for at least 6 months were enrolled. Participants were randomized to treatment with either nortiptyline or placebo. In both groups, dosing was escalated at 3-week intervals (10, 25, 50, 75 mg) up to 75 mg at 12 weeks. At follow-up study visits, which occurred every 3 weeks, symptom questionnaires were administered to assess gastrointestinal and psychological symptoms, quality of life, and TCA side effects. Electrogastrography (EGG) satiety tests and electrocardiography tests were also performed. Treatment was continued for 15 weeks, at which time study medication dose was tapered to zero with a final assessment at 18 weeks. The primary outcome measure was a decrease from the patient’s baseline Gastroparesis Cardinal Symptom Index (GCSI) score of at least 50% on two consecutive 3 week GCSI assessments over 15 weeks of treatment. Secondary outcome measures included physiological assessments during satiety testing, clinical and psychological symptom scores, and adverse event rates.
Overall symptomatic improvement, as defined by the primary outcome measure, did not differ between the treatment groups: 23% on nortriptyline versus 21% on placebo. Additionally, treatment with nortriptyline showed no improvement in nausea, fullness/satiety, bloating, or quality of life measures. These findings suggest that TCAs may not be effective in the treatment of idiopathic gastroparesis.
The NORIG study tested whether treatment with nortriptyline, a TCA with reduced anticholinergic side effects, results in symptomatic improvement in patients with idiopathic gastroparesis.
The primary outcome measure was a decrease from the patient’s baseline Gastroparesis Cardinal Symptom Index (GCSI) score of at least 50% on two consecutive 3 week GCSI assessments over 15 weeks of treatment. Secondary outcome measures included physiological assessments during satiety testing, clinical and psychological symptom scores, and adverse event rates.
Individuals between the ages of 21 and 68 years old who met the following criteria were eligible for the study:
Patients having dyspeptic symptoms with normal gastric emptying or having diabetic gastroparesis or post-surgical gastroparesis including fundoplication were excluded.
Overall symptomatic improvement, as defined by the primary outcome measure, did not differ between the treatment groups: 23% on nortriptyline versus 21% on placebo. Additionally, treatment with nortriptyline showed no improvement in nausea, fullness/satiety, bloating, or quality of life measures. These findings suggest that TCAs may not be effective in the treatment of idiopathic gastroparesis.
Digestive Diseases
Interventional
7
2009-01
2012-10
Gastroparesis
Gastric Emptying, Tricylcic Antidepressants, Nortripytline, Gastroparesis, Calcium Channel, Gastroparesis Cardinal Symptom Index (GCSI)
Division of Digestive Diseases and Nutrition
Document Name | Description | Document Type | File Format |
---|---|---|---|
NORIG Informed Consent Statement | NORIG Informed Consent Statement provided by the NIH, GpCRC, and NORIG | Consent Form Template | |
NORIG Genetic Informed Consent Statement | NORIG Informed Consent Statement for the collection storage, and use of blood samples for current and future genetic research provided by the NIH, GpCRC, and NORIG | Consent Form Template | |
Dataset Name | Description | # of Records | # of Variables | File Format(s) |
---|---|---|---|---|
GD1 Form Dataset | Contains data from the Patient Assessment of Gastrointestinal Disorders - Symptom Severity Index form | 854 | sas7bdat (64 KB); csv (120.45 KB) | |
Treatment Randomization Groups Dataset | Contains the randomization groups for the subjects in the NORIG trial | 130 | sas7bdat (16 KB); csv (2.05 KB) | |
RG2 Form Dataset | Contains data from the Registration form | 130 | sas7bdat (40 KB); csv (13.83 KB) | |
PQ1 Form Dataset | Contains data from the Patient Health Questionnaire form | 367 | sas7bdat (24 KB); csv (27.75 KB) | |
SE1 Form Dataset | Contains data from the State-Trait Anxiety Inventory form | 366 | sas7bdat (24 KB); csv (9.69 KB) | |
FH1 Form Dataset | Contains data from the Follow-Up Medical History form | 725 | sas7bdat (408 KB); csv (386.49 KB) | |
BH2 Form Dataset | Contains data from the Baseline Medical History form | 130 | sas7bdat (88 KB); csv (71.47 KB) | |
GE1 Form Dataset | Contains data from the Gastric Emptying Scintigraphy Documentation form | 130 | sas7bdat (72 KB); csv (19.71 KB) | |
IE1 Form Dataset | Contains data from the Interim Event Report form | 108 | sas7bdat (56 KB); csv (19.64 KB) | |
RD1 Form Dataset | Contains data from the Study Drug Dispensing and Return form | 879 | sas7bdat (136 KB); csv (92.89 KB) | |
QF1 Form Dataset | Contains data from the SF-36v2 Health Survey form | 366 | sas7bdat (40 KB); csv (57.88 KB) | |
LR1 Form Dataset | Contains data from the Laboratory Results form | 243 | sas7bdat (72 KB); csv (39.5 KB) | |
GS1 Form Dataset | Contains data from the Gastrointestinal Symptom Rating Scale (GSRS) form | 854 | sas7bdat (40 KB); csv (64.47 KB) | |
PI1 Form Dataset | Contains data from the Brief Pain Inventory form | 367 | sas7bdat (72 KB); csv (33.92 KB) | |
DD1 Form Dataset | Contains data from the Drug Dosing Determination and Dispensing form | 741 | sas7bdat (40 KB); csv (47.36 KB) | |
ST3 Form Dataset | Contains data from the ECG and Satiety Test form | 278 | sas7bdat (136 KB); csv (163.71 KB) | |
EG1 Form Dataset | Contains data from the Upper Endoscopy Documentation form | 130 | sas7bdat (56 KB); csv (21.59 KB) | |
PE2 Form Dataset | Contains data from the Physical Examination form | 509 | sas7bdat (248 KB); csv (104.64 KB) | |
BD1 Form Dataset | Contains data from the Beck Depression Inventory form | 854 | sas7bdat (32 KB); csv (28.52 KB) | |
Specimen | Count |
---|---|
Plasma | 2285 |
Serum | 10 |