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

January 5, 2016 updated by: Adil Bharucha, Mayo Clinic

A Pilot Study of Hemin Therapy for Gastroparesis

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).

Study Overview

Status

Completed

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

Enrollment (Actual)

20

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Minnesota
      • Rochester, Minnesota, United States, 55901
        • Mayo Clinic

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 68 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

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

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

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2010

Primary Completion (Actual)

December 1, 2014

Study Completion (Actual)

December 1, 2014

Study Registration Dates

First Submitted

September 20, 2010

First Submitted That Met QC Criteria

September 21, 2010

First Posted (Estimate)

September 22, 2010

Study Record Updates

Last Update Posted (Estimate)

February 4, 2016

Last Update Submitted That Met QC Criteria

January 5, 2016

Last Verified

January 1, 2016

More Information

Terms related to this study

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.

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