GastroparesisPhase 2NCT01206582
A Pilot Study of Hemin Therapy for Gastroparesis (Diabetes Mellitus)
A Phase 2 study testing Hemin and Albumin in people with Gastroparesis and Diabetes Mellitus, run by Mayo Clinic at 1 site in United States.
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). Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Gastroparesis, Diabetes Mellitus
- What is being tested?
- Hemin and Albumin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- May 2010to Dec 2014
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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).
Read the 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.
- Conditions
- Gastroparesis, Diabetes Mellitus
- Being tested
- Hemin, Albumin
- Medical subject headings
- Gastroparesis, Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HeminBiological
Also called Panhematin®, (Ovation Pharmaceuticals, Deerfield, IL)
10 iv infusions for 8 weeks
AlbuminBiological
Also called Albumin (Human) 25% Solution manufactured by CSL Behring.
10 iv infusions for 8 weeks
| Study group | Role | What they receive |
|---|---|---|
| Hemin | Active comparator | 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 Receives: Biological: Hemin |
| Albumin | Placebo comparator | 10 iv infusions for 8 weeks Receives: Biological: Albumin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: baseline, day 3, day 7, day 56
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.
Measured: baseline, Day 3, Day 7, Day 56
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.
Measured: baseline, day 3, day 7, day 56
Secondary outcomes (8)
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.
Measured: baseline, 8 weeks
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.
Measured: baseline, Day 56
Serum Creatinine
Measured: baseline, Day 4, Day 7, Day 56
Prothrombin Time
Measured: baseline, Day 4, Day 7, Day 56
Activated Partial Thromboplastin Time (APTT)
Measured: baseline, Day 4, Day 7, Day 56
Hemoglobin
Measured by complete blood count
Measured: baseline, Day 4, Day 7, Day 56
Erythrocyte Count
Measured by complete blood count
Measured: baseline, Day 4, Day 7, Day 56
Leukocyte and Platelet Counts
Measured by complete blood count
Measured: baseline, Day 4, Day 7, Day 56
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Sep 2010 (estimated)
- Study startMay 2010
- Primary completionDec 2014
- Study completionDec 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for GastroparesisStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), RECORDATI GROUP
- Responsible party
- Principal investigator, Adil Bharucha, Mayo Clinic
- Investigators
- Adil E Bharucha, MBBS, MD, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01206582
- Sponsor's protocol ID
- 09-000129
- Other IDs
- P01DK068055, UL1TR000135
- Status last verified
- Jan 2016
- First submitted
- 20 Sep 2010
- Last updated
- 4 Feb 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of Hemin Therapy for Gastroparesis
- ClinicalTrials.gov ID
- NCT01206582
- Acronym / sponsor ID
- 09-000129
- Conditions
- Gastroparesis, Diabetes Mellitus
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), RECORDATI GROUP
- Study start
- May 2010
- Primary completion
- Dec 2014 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 22 Sep 2010 (estimated)
- Results
- Posted 4 Feb 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Hemin | Active comparator | Biological: HeminPanhematin®, 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 |
| Albumin | Placebo comparator | Biological: Albumin10 iv infusions for 8 weeks |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HeminAlso: Panhematin®, (Ovation Pharmaceuticals, Deerfield, IL)10 iv infusions for 8 weeks | Biological | Hemin |
| AlbuminAlso: Albumin (Human) 25% Solution manufactured by CSL Behring.10 iv infusions for 8 weeks | Biological | Albumin |
Primary outcome
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.
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.
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.
8 secondary outcomes
Gastrointestinal Symptoms
Time frame: baseline, 8 weeks
Autonomic Functions
Time frame: baseline, Day 56
Serum Creatinine
Time frame: baseline, Day 4, Day 7, Day 56
Prothrombin Time
Time frame: baseline, Day 4, Day 7, Day 56
Activated Partial Thromboplastin Time (APTT)
Time frame: baseline, Day 4, Day 7, Day 56
Hemoglobin
Time frame: baseline, Day 4, Day 7, Day 56
Erythrocyte Count
Time frame: baseline, Day 4, Day 7, Day 56
Leukocyte and Platelet Counts
Time frame: baseline, Day 4, Day 7, Day 56
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Feb 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Adil E Bharucha, MBBS, MD principal investigator
Mayo Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Hemin and Albumin in people with Gastroparesis and Diabetes Mellitus, run by Mayo Clinic at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Feb 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Venous Plasma Heme-oxygenase 1 (HO1) Protein Concentration (time frame: baseline, day 3, day 7, day 56). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Feb 2016.