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

• - Heme-oxygenase 1 (HO-1) protein concentration [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
• - HO-1 activity [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
• Gastric emptying by scintigraphy [ Time Frame: 8 weeks (or last completed assessment) ] [ Designated as safety issue: No ]
• - Gastrointestinal symptoms [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]

• HO-1 protein concentration [ Time Frame: 1, 3, 4, 7, 14, 21, 28, 35, 42, and 49 days ] [ Designated as safety issue: No ]
• Gastric emptying [ Time Frame: days 1, 4, 7, 14, 21, 28, 35, 42, and 49 ] [ Designated as safety issue: No ]
• Gastrointestinal symptoms [ Time Frame: days 1, 4, 7, 14, 21, 28, 35, 42, and 49. ] [ Designated as safety issue: No ]
• Autonomic functions [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
• Serum chemistry [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]
  Includes serum creatinine and transaminases
• coagulation parameters [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]
  Includes PT and APTT
• hematological parameters [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]
  complete blood count

This study is designed to learn if hemin can increase the production of heme oxygenase 1 and improve gastric (stomach) emptying and symptoms in patients with slow gastric emptying (gastroparesis).

Heme oxygenase 1 (HO-1) 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.

• Gastroparesis
• Diabetes Mellitus

• Biological: Hemin
  10 iv infusions for 8 weeks
  Other Name: Panhematin®, (Ovation Pharmaceuticals, Deerfield, IL)
• Biological: Albumin (25%)
  10 iv infusions for 8 weeks
  Other Name: Albumin (Human) 25% Solution manufactured by CSL Behring.

• Active Comparator: Hemin
  Panhematin®, Ovation Pharmaceuticals, Deerfield, IL
  Intervention: Biological: Hemin
• Placebo Comparator: Albumin (25%)
  Intervention: Biological: Albumin (25%)

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