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

Diabetes Mellitus Clinical Trial

Official title:

A Pilot Study of Hemin Therapy for Gastroparesis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01206582
• Other study ID #: 09-000129
• Secondary ID: P01DK068055UL1TR
• Status: Completed
• Phase: Phase 2
• First received: September 20, 2010
• Last updated: January 5, 2016
• Start date: May 2010
• Est. completion date: December 2014

Study information

• Verified date: January 2016
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: December 2014
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus
• Gastroparesis

Intervention

Biological:
• Hemin
10 iv infusions for 8 weeks
• Albumin
10 iv infusions for 8 weeks

Locations

Country	Name	City	State
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (3)

Lead Sponsor	Collaborator
Mayo Clinic	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Recordati Rare Diseases

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Venous Plasma Heme-oxygenase 1 (HO1) Protein Concentration	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	No
Primary	Venous Monocyte HO1 Activity	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	No
Primary	Gastric Emptying Half-time	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	No
Secondary	Gastrointestinal Symptoms	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	No
Secondary	Autonomic Functions	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	No
Secondary	Serum Creatinine		baseline, Day 4, Day 7, Day 56	Yes
Secondary	Prothrombin Time		baseline, Day 4, Day 7, Day 56	Yes
Secondary	Activated Partial Thromboplastin Time (APTT)		baseline, Day 4, Day 7, Day 56	Yes
Secondary	Hemoglobin	Measured by complete blood count	baseline, Day 4, Day 7, Day 56	Yes
Secondary	Erythrocyte Count	Measured by complete blood count	baseline, Day 4, Day 7, Day 56	Yes
Secondary	Leukocyte and Platelet Counts	Measured by complete blood count	baseline, Day 4, Day 7, Day 56	Yes