This study is designed to learn if hemin can increase the production of heme oxygenase 1 and improve gastric (stomach) emptying and symptoms in diabetic patients with slow gastric emptying (gastroparesis).
Therapeutic options for management of diabetic gastroparesis are limited. Failure to maintain upregulation of heme oxygenase 1 (HO1) leads to loss of interstitial cells of Cajal and delayed gastric emptying in diabetic non-obese diabetic mice. HO1 is an enzyme which protects cells from physical, chemical, and biologic stress. In mice with diabetes and slow gastric emptying, hemin increases HO-1 activity and improves gastric emptying. Hemin is produced from red blood cells and is approved by the Food and Drug Administration for treating acute porphyria, which is an inherited condition caused by an enzyme deficiency. Hemin is not approved by the Food and Drug Administration for treating gastroparesis. In this study subjects were randomized to intravenous hemin, prepared in albumin, or albumin alone. After infusions on days 1, 3, and 7, weekly infusions were administered for 7 weeks. Assessments included blood tests for HO1 protein and enzyme activity levels, gastric emptying with 13\^C-spirulina breath test, autonomic functions (baseline and end), and gastrointestinal symptoms every 2 weeks.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
20
Mayo Clinic
Rochester, Minnesota, United States
Venous Plasma Heme-oxygenase 1 (HO1) Protein Concentration
HO1 protein concentration levels in plasma were assessed with a HO1 (human) enzyme-linked immunosorbent assay (ELISA) kit.
Time frame: baseline, day 3, day 7, day 56
Venous Monocyte HO1 Activity
HO1 activity in white blood cells was measured by an assay that measures bilirubin production as a marker of HO1 activity.
Time frame: baseline, Day 3, Day 7, Day 56
Gastric Emptying Half-time
The time for half of the ingested solids or liquids to leave the stomach. Gastric emptying was assessed with \^13C Spirulina Breath Test. After an overnight fast, subjects consumed the test meal containing \^13C Spirulina. Breath samples were collected in duplicate glass tube using a straw to blow into the bottom of the tube to displace contained air. The \^13CO\_2 content of the breath was determined by AB Diagnostics. The provide of \^13CO\_2 excretion is used to estimate the half-time of gastric emptying.
Time frame: baseline, day 3, day 7, day 56
Gastrointestinal Symptoms
Subjects recorded their GI symptoms every day in the validated Gastroparesis Cardinal Symptom Index (GCSI) - Daily Diary. For each subject, the daily GCSI data were averaged per week. Components coded 0 (no symptoms) to 5 (very severe). GCSI total score is the average of 9 components from the nausea/vomiting, fullness/early satiety, and bloating subscores. These individual subscores are averages of 3,4, and 2 components, respectively. Subscores for upper and lower abdominal pain, heartburn/regurgitation and FDA nausea, vomiting, fullness, and pain (NVFP) composite are averages of 2, 2, 7, and 4 components, respectively.
Time frame: baseline, 8 weeks
Autonomic Functions
Subjects completed a standardized autonomic symptom questionnaire, the Composite Autonomic Severity Score (CASS) which consists of 2 subscores: cardiovagal (CASS-vag; 0-3) and adrenergic (CASS-adr;0-3), where 0, 1, 2, 3 represent non, mild, moderate, and severe dysfunction, respectively.
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Time frame: baseline, Day 56
Serum Creatinine
Time frame: baseline, Day 4, Day 7, Day 56
Prothrombin Time
Time frame: baseline, Day 4, Day 7, Day 56
Activated Partial Thromboplastin Time (APTT)
Time frame: baseline, Day 4, Day 7, Day 56
Hemoglobin
Measured by complete blood count
Time frame: baseline, Day 4, Day 7, Day 56
Erythrocyte Count
Measured by complete blood count
Time frame: baseline, Day 4, Day 7, Day 56
Leukocyte and Platelet Counts
Measured by complete blood count
Time frame: baseline, Day 4, Day 7, Day 56