A Pilot Study of Hemin Therapy for Gastroparesis (Diabetes Mellitus)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01206582
Recruitment Status : Completed
First Posted : September 22, 2010
Results First Posted : February 4, 2016
Last Update Posted : February 4, 2016
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Recordati Rare Diseases
Information provided by (Responsible Party):
Adil Bharucha, Mayo Clinic

Brief Summary:
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).

Condition or disease Intervention/treatment Phase
Gastroparesis Diabetes Mellitus Biological: Hemin Biological: Albumin Phase 2

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 : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by the National Library of Medicine

Drug Information available for: Hemin

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
Biological: Hemin
10 iv infusions for 8 weeks
Other Name: Panhematin®, (Ovation Pharmaceuticals, Deerfield, IL)

Placebo Comparator: Albumin
10 iv infusions for 8 weeks
Biological: Albumin
10 iv infusions for 8 weeks
Other Name: Albumin (Human) 25% Solution manufactured by CSL Behring.

Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. Serum Creatinine [ Time Frame: baseline, Day 4, Day 7, Day 56 ]
  4. Prothrombin Time [ Time Frame: baseline, Day 4, Day 7, Day 56 ]
  5. Activated Partial Thromboplastin Time (APTT) [ Time Frame: baseline, Day 4, Day 7, Day 56 ]
  6. Hemoglobin [ Time Frame: baseline, Day 4, Day 7, Day 56 ]
    Measured by complete blood count

  7. Erythrocyte Count [ Time Frame: baseline, Day 4, Day 7, Day 56 ]
    Measured by complete blood count

  8. Leukocyte and Platelet Counts [ Time Frame: baseline, Day 4, Day 7, Day 56 ]
    Measured by complete blood count

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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 (

  • 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

Information from the National Library of Medicine

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 identifier (NCT number): NCT01206582

United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55901
Sponsors and Collaborators
Mayo Clinic
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Recordati Rare Diseases
Principal Investigator: Adil E Bharucha, MBBS, MD Mayo Clinic

Responsible Party: Adil Bharucha, PI, Mayo Clinic Identifier: NCT01206582     History of Changes
Other Study ID Numbers: 09-000129
P01DK068055 ( U.S. NIH Grant/Contract )
UL1TR000135 ( U.S. NIH Grant/Contract )
First Posted: September 22, 2010    Key Record Dates
Results First Posted: February 4, 2016
Last Update Posted: February 4, 2016
Last Verified: January 2016

Additional relevant MeSH terms:
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Stomach Diseases
Gastrointestinal Diseases
Digestive System Diseases
Neurologic Manifestations
Signs and Symptoms