Clinical trial NCT01206582: A Pilot Study of Hemin Therapy for Gastroparesis (Diabetes Mellitus)
Official title: A Pilot Study of Hemin Therapy for Gastroparesis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Gastroparesis
Diabetes Mellitus
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
name: Recordati Rare Diseases
First posted: 2010-09-22
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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.

Eligibility criteria: 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

Primary outcomes:
measure: Venous Plasma Heme-oxygenase 1 (HO1) Protein Concentration
timeFrame: baseline, day 3, day 7, day 56
measure: Venous Monocyte HO1 Activity
timeFrame: baseline, Day 3, Day 7, Day 56
measure: Gastric Emptying Half-time
timeFrame: baseline, day 3, day 7, day 56
Secondary outcomes:
measure: Gastrointestinal Symptoms
timeFrame: baseline, 8 weeks
measure: Autonomic Functions
timeFrame: baseline, Day 56
measure: Serum Creatinine
timeFrame: baseline, Day 4, Day 7, Day 56
measure: Prothrombin Time
timeFrame: baseline, Day 4, Day 7, Day 56
measure: Activated Partial Thromboplastin Time (APTT)
timeFrame: baseline, Day 4, Day 7, Day 56
measure: Hemoglobin
timeFrame: baseline, Day 4, Day 7, Day 56
measure: Erythrocyte Count
timeFrame: baseline, Day 4, Day 7, Day 56
measure: Leukocyte and Platelet Counts
timeFrame: baseline, Day 4, Day 7, Day 56
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Adil E Bharucha, MBBS, MD
role: PRINCIPAL_INVESTIGATOR
References: