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

NCT ID: NCT01206582

Last Updated: 2016-02-04

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-05-31

Study Completion Date

2014-12-31

Brief Summary

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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

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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.

Conditions

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Gastroparesis Diabetes Mellitus

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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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

Group Type ACTIVE_COMPARATOR

Hemin

Intervention Type BIOLOGICAL

10 iv infusions for 8 weeks

Albumin

10 iv infusions for 8 weeks

Group Type PLACEBO_COMPARATOR

Albumin

Intervention Type BIOLOGICAL

10 iv infusions for 8 weeks

Interventions

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Hemin

10 iv infusions for 8 weeks

Intervention Type BIOLOGICAL

Albumin

10 iv infusions for 8 weeks

Intervention Type BIOLOGICAL

Other Intervention Names

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Panhematin®, (Ovation Pharmaceuticals, Deerfield, IL) Albumin (Human) 25% Solution manufactured by CSL Behring.

Eligibility Criteria

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Exclusion Criteria

* 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.


* 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
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role collaborator

Recordati Rare Diseases

INDUSTRY

Sponsor Role collaborator

Mayo Clinic

OTHER

Sponsor Role lead

Responsible Party

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Adil Bharucha

PI

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Adil E Bharucha, MBBS, MD

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

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Mayo Clinic

Rochester, Minnesota, United States

Site Status

Countries

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United States

Other Identifiers

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P01DK068055

Identifier Type: NIH

Identifier Source: secondary_id

View Link

UL1TR000135

Identifier Type: NIH

Identifier Source: secondary_id

View Link

09-000129

Identifier Type: -

Identifier Source: org_study_id

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