A Pilot Study of Hemin Therapy for Gastroparesis (Diabetes Mellitus)
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|ClinicalTrials.gov Identifier: NCT01206582|
Recruitment Status : Completed
First Posted : September 22, 2010
Results First Posted : February 4, 2016
Last Update Posted : February 4, 2016
|Condition or disease||Intervention/treatment||Phase|
|Gastroparesis Diabetes Mellitus||Biological: Hemin Biological: Albumin||Phase 2|
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 (Clinical Trial)|
|Actual Enrollment :||20 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||A Pilot Study of Hemin Therapy for Gastroparesis|
|Study Start Date :||May 2010|
|Actual Primary Completion Date :||December 2014|
|Actual Study Completion Date :||December 2014|
Active Comparator: Hemin
Panhematin®, Ovation Pharmaceuticals, Deerfield, Illinois (IL). Hemin was diluted in 25% albumin to obtain a concentration of 2.4 mg/mL and administered at a dose of 1.25 mL/Kg and at a rate of 60 mL/hour. 10 iv infusions for 8 weeks
10 iv infusions for 8 weeks
Other Name: Panhematin®, (Ovation Pharmaceuticals, Deerfield, IL)
Placebo Comparator: Albumin
10 iv infusions for 8 weeks
10 iv infusions for 8 weeks
Other Name: Albumin (Human) 25% Solution manufactured by CSL Behring.
- Venous Plasma Heme-oxygenase 1 (HO1) Protein Concentration [ Time Frame: baseline, day 3, day 7, day 56 ]HO1 protein concentration levels in plasma were assessed with a HO1 (human) enzyme-linked immunosorbent assay (ELISA) kit.
- Venous Monocyte HO1 Activity [ Time Frame: baseline, Day 3, Day 7, Day 56 ]HO1 activity in white blood cells was measured by an assay that measures bilirubin production as a marker of HO1 activity.
- Gastric Emptying Half-time [ Time Frame: baseline, day 3, day 7, day 56 ]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.
- Gastrointestinal Symptoms [ Time Frame: baseline, 8 weeks ]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.
- Autonomic Functions [ Time Frame: baseline, Day 56 ]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.
- 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 [ Time Frame: baseline, Day 4, Day 7, Day 56 ]Measured by complete blood count
- Erythrocyte Count [ Time Frame: baseline, Day 4, Day 7, Day 56 ]Measured by complete blood count
- Leukocyte and Platelet Counts [ Time Frame: baseline, Day 4, Day 7, Day 56 ]Measured by complete blood count
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01206582
|United States, Minnesota|
|Rochester, Minnesota, United States, 55901|
|Principal Investigator:||Adil E Bharucha, MBBS, MD||Mayo Clinic|