- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01206582
A Pilot Study of Hemin Therapy for Gastroparesis (Diabetes Mellitus)
A Pilot Study of Hemin Therapy for Gastroparesis
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
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
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Minnesota
-
Rochester, Minnesota, United States, 55901
- Mayo Clinic
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
Where relevant (i.e., for ensuring safety), the inclusion and exclusion criteria are similar to those in a recently completed trial of hemin therapy for myelodysplastic syndrome at Rush University, Chicago (http://clinicaltrials.gov/ct2/show/NCT00467610).
- Upper gastrointestinal symptoms which satisfy criteria for postprandial distress syndrome or vomiting for the last 3 months with symptom onset at least 6 months prior to diagnosis
- At least moderately severe symptoms as manifest by a total symptom score of 2.5 or higher on the Gastroparesis Cardinal Symptom Index (GCSI)21
- Delayed gastric emptying (i.e, < 40% emptying at 2 and/or < 90% emptying at 4 hours by scintigraphy)
- No structural cause for symptoms by endoscopy within the past 12 months
- Patient must have a platelet counts > 50,000/microliters and absolute neutrophil counts (ANC) >500/microliters.
- Patient must have adequate hepatic and renal functions, defined as serum bilirubin, serum glutamic-oxaloacetic transaminase (SGOT), and serum glutamate pyruvate transaminase (SGPT) ≤ 2 times the upper limit of normal (ULN), and creatinine ≤ 1.5 times the ULN.
- Able to provide written informed consent before participating in the study
If female:
- Either not of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy), or if of childbearing potential, must comply with an effective method of birth control acceptable to the investigator during the study (oral contraceptives, Depo-Provera, intra-uterine device or barrier methods)
- Patient is not breastfeeding.
- Patient of childbearing potential must have a negative urine or serum pregnancy test during the screening period.
Exclusion Criteria:
- History of allergic reaction or significant sensitivity to Panhemantin ®
- Patients who have taken or used any investigational drug or device in the 30 days prior to screening
- Predominant symptoms of epigastric pain or rumination syndrome
- Structural cause for symptoms on recent endoscopy
- Patients with preexisting blood coagulation abnormalities
- Patients with previously documented renal impairment defined as above 150 mmol/L or 1.7 mg/dL serum creatinine
- Previous gastric or intestinal surgery - patients with enteral feeding tubes and/or venting/feeding gastrostomy will be eligible provided they can comply with study requirements. Tube feeding will be stopped 24 hours before the gastric emptying study
- Current use of narcotics, anticholinergic agents (e.g., hyoscyamine, belladonna), anticoagulants (e.g., warfarin) or erythromycin. Gastrointestinal prokinetic drugs (eg metoclopramide, or domperidone) may be continued at a stable dose throughout the study
- History of a pre-existing medical condition that, in the opinion of the investigator, will interfere with the participation in the study.
- History of venous thrombosis or hypercoagulable state
- Poor peripheral venous access, if central venous access is not available
- Uncontrolled active infection
- Any other condition or prior therapy that, in the opinion of the investigator, would make the patient unsuitable for the study.
- Known intolerance or allergy to eggs
- Screening weight greater than 130 kg
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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 Names:
|
Placebo Comparator: Albumin
10 iv infusions for 8 weeks
|
10 iv infusions for 8 weeks
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
baseline, day 3, day 7, day 56
|
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.
|
baseline, Day 3, Day 7, Day 56
|
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.
|
baseline, day 3, day 7, day 56
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
baseline, 8 weeks
|
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.
|
baseline, Day 56
|
Serum Creatinine
Time Frame: baseline, Day 4, Day 7, Day 56
|
baseline, Day 4, Day 7, Day 56
|
|
Prothrombin Time
Time Frame: baseline, Day 4, Day 7, Day 56
|
baseline, Day 4, Day 7, Day 56
|
|
Activated Partial Thromboplastin Time (APTT)
Time Frame: baseline, Day 4, Day 7, Day 56
|
baseline, Day 4, Day 7, Day 56
|
|
Hemoglobin
Time Frame: baseline, Day 4, Day 7, Day 56
|
Measured by complete blood count
|
baseline, Day 4, Day 7, Day 56
|
Erythrocyte Count
Time Frame: baseline, Day 4, Day 7, Day 56
|
Measured by complete blood count
|
baseline, Day 4, Day 7, Day 56
|
Leukocyte and Platelet Counts
Time Frame: baseline, Day 4, Day 7, Day 56
|
Measured by complete blood count
|
baseline, Day 4, Day 7, Day 56
|
Collaborators and Investigators
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 09-000129
- UL1TR000135 (U.S. NIH Grant/Contract)
- P01DK068055 (U.S. NIH Grant/Contract)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Diabetes Mellitus
-
University of Colorado, DenverMassachusetts General Hospital; Beta Bionics, Inc.CompletedDiabetes Mellitus, Type 1 | Type 1 Diabetes | Diabetes type1 | Type 1 Diabetes Mellitus | Autoimmune Diabetes | Diabetes Mellitus, Insulin-Dependent | Juvenile-Onset Diabetes | Diabetes, Autoimmune | Insulin-Dependent Diabetes Mellitus 1 | Diabetes Mellitus, Insulin-Dependent, 1 | Diabetes Mellitus, Brittle | Diabetes Mellitus, Juvenile-Onset and other conditionsUnited States
-
Guang NingRecruitingType 2 Diabetes Mellitus | Type1 Diabetes Mellitus | Monogenetic Diabetes | Pancreatogenic Diabetes | Drug-Induced Diabetes Mellitus | Other Forms of Diabetes MellitusChina
-
Meir Medical CenterCompletedDiabetes Mellitus Type 2 | Diabetes Mellitus, Non-insulin Dependant | Diabetes Mellitus, on Oral Hypoglycemic Treatment | Adult Type Diabetes MellitusIsrael
-
Peking Union Medical College HospitalUnknownType 2 Diabetes Mellitus | Type 1 Diabetes Mellitus | Gestational Diabetes Mellitus | Pancreatogenic Diabetes Mellitus | Pregestational Diabetes Mellitus | Diabetes Patients in Perioperative PeriodChina
-
Medical College of WisconsinMedical University of South CarolinaCompletedDiabetes Mellitus | Type 2 Diabetes Mellitus | Adult-Onset Diabetes Mellitus | Non-Insulin-Dependent Diabetes Mellitus | Noninsulin Dependent Diabetes Mellitus, Type IIUnited States
-
Hanmi Pharmaceutical Company LimitedUnknownType2 Diabetes Mellitus | Type1 Diabetes MellitusUnited States
-
Medical College of WisconsinMedical University of South Carolina; National Institute of Diabetes and Digestive...Active, not recruitingDiabetes Mellitus, Type 2 | Diabetes Mellitus, Type II | Diabetes Mellitus, Adult-Onset | Diabetes Mellitus, Non-Insulin-Dependent | Diabetes Mellitus, Noninsulin DependentUnited States
-
Medical College of WisconsinNational Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)CompletedDiabetes Mellitus, Type 2 | Diabetes Mellitus, Type II | Diabetes Mellitus, Adult-Onset | Diabetes Mellitus, Non-Insulin-Dependent | Diabetes Mellitus, Noninsulin DependentUnited States
-
Joslin Diabetes CenterCambridge Medical Technologies, LLCCompletedType 2 Diabetes Mellitus | Type1 Diabetes MellitusUnited States
-
SanofiCompletedType 1 Diabetes Mellitus-Type 2 Diabetes MellitusHungary, Russian Federation, Germany, Poland, Japan, United States, Finland
Clinical Trials on Hemin
-
The University of Texas Medical Branch, GalvestonActive, not recruitingHereditary Coproporphyria | Acute Intermittent Porphyria | Variegate PorphyriaUnited States
-
The University of Texas Medical Branch, GalvestonRecruitingHereditary Coproporphyria | Acute Intermittent Porphyria | Variegate PorphyriaUnited States
-
Erasme University HospitalCompletedPost-ERCP Acute PancreatitisTaiwan, Belgium
-
University of EdinburghNHS LothianCompletedIschemia-reperfusion Injury | Graft FailureUnited Kingdom