Trial Outcomes & Findings for A Pilot Study of Hemin Therapy for Gastroparesis (Diabetes Mellitus) (NCT NCT01206582)
NCT ID: NCT01206582
Last Updated: 2016-02-04
Results Overview
HO1 protein concentration levels in plasma were assessed with a HO1 (human) enzyme-linked immunosorbent assay (ELISA) kit.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
20 participants
Primary outcome timeframe
baseline, day 3, day 7, day 56
Results posted on
2016-02-04
Participant Flow
Subjects were enrolled at Mayo Clinic in Rochester, Minnesota between Mayo 2010 and November 2013.
Participant milestones
| Measure |
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
|
Albumin
10 iv infusions for 8 weeks
|
|---|---|---|
|
Overall Study
STARTED
|
11
|
9
|
|
Overall Study
COMPLETED
|
9
|
7
|
|
Overall Study
NOT COMPLETED
|
2
|
2
|
Reasons for withdrawal
| Measure |
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
|
Albumin
10 iv infusions for 8 weeks
|
|---|---|---|
|
Overall Study
Withdrew prior to study
|
1
|
0
|
|
Overall Study
Discontinued intervention before week 8
|
1
|
2
|
Baseline Characteristics
A Pilot Study of Hemin Therapy for Gastroparesis (Diabetes Mellitus)
Baseline characteristics by cohort
| Measure |
Hemin
n=11 Participants
Panhematin®, Ovation Pharmaceuticals, Deerfield, 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
n=9 Participants
10 iv infusions for 8 weeks
|
Total
n=20 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
45.9 years
STANDARD_DEVIATION 14.4 • n=5 Participants
|
35.2 years
STANDARD_DEVIATION 14.9 • n=7 Participants
|
41.1 years
STANDARD_DEVIATION 15.3 • n=5 Participants
|
|
Sex: Female, Male
Female
|
9 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
11 participants
n=5 Participants
|
9 participants
n=7 Participants
|
20 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: baseline, day 3, day 7, day 56Population: Total number of subjects analyzed varied per time period due to discontinuations, subject and data availability. Subjects analyzed are presented per category as (n=hemin, albumin arms).
HO1 protein concentration levels in plasma were assessed with a HO1 (human) enzyme-linked immunosorbent assay (ELISA) kit.
Outcome measures
| Measure |
Hemin
n=11 Participants
Panhematin®, Ovation Pharmaceuticals, Deerfield, 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
n=9 Participants
10 iv infusions for 8 weeks
|
|---|---|---|
|
Venous Plasma Heme-oxygenase 1 (HO1) Protein Concentration
baseline (n=11, 8)
|
1.6 ng/mL
Standard Error 0.3
|
1.5 ng/mL
Standard Error 0.1
|
|
Venous Plasma Heme-oxygenase 1 (HO1) Protein Concentration
Day 3 (n=10, 8)
|
10.6 ng/mL
Standard Error 2.3
|
1.5 ng/mL
Standard Error 0.3
|
|
Venous Plasma Heme-oxygenase 1 (HO1) Protein Concentration
Day 7 (n=8, 8)
|
7.0 ng/mL
Standard Error 2.1
|
1.2 ng/mL
Standard Error 0.2
|
|
Venous Plasma Heme-oxygenase 1 (HO1) Protein Concentration
Day 56 (n=9, 4)
|
2.6 ng/mL
Standard Error 0.8
|
1.0 ng/mL
Standard Error 0.1
|
PRIMARY outcome
Timeframe: baseline, Day 3, Day 7, Day 56Population: Total number of subjects analyzed varied per time period due to discontinuations, subject and data availability. Subjects analyzed are presented per category as (n=hemin, albumin arms).
HO1 activity in white blood cells was measured by an assay that measures bilirubin production as a marker of HO1 activity.
Outcome measures
| Measure |
Hemin
n=11 Participants
Panhematin®, Ovation Pharmaceuticals, Deerfield, 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
n=9 Participants
10 iv infusions for 8 weeks
|
|---|---|---|
|
Venous Monocyte HO1 Activity
Day 56 (n=8, 4)
|
30.1 pmol bilirubin/mg/h
Standard Error 12.7
|
60.1 pmol bilirubin/mg/h
Standard Error 23.0
|
|
Venous Monocyte HO1 Activity
Baseline (n=10, 8)
|
38.5 pmol bilirubin/mg/h
Standard Error 12.0
|
42.1 pmol bilirubin/mg/h
Standard Error 10.9
|
|
Venous Monocyte HO1 Activity
Day 3 (n=9, 8)
|
373.9 pmol bilirubin/mg/h
Standard Error 82.8
|
48.1 pmol bilirubin/mg/h
Standard Error 12.9
|
|
Venous Monocyte HO1 Activity
Day 7 (n=8, 8)
|
126.2 pmol bilirubin/mg/h
Standard Error 51.3
|
36.1 pmol bilirubin/mg/h
Standard Error 12.0
|
PRIMARY outcome
Timeframe: baseline, day 3, day 7, day 56Population: Total number of subjects analyzed varied per time period due to discontinuations, subject and data availability. Subjects analyzed are presented per category as (n=hemin, albumin arms).
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.
Outcome measures
| Measure |
Hemin
n=11 Participants
Panhematin®, Ovation Pharmaceuticals, Deerfield, 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
n=9 Participants
10 iv infusions for 8 weeks
|
|---|---|---|
|
Gastric Emptying Half-time
Baseline (n=10, 9)
|
161.8 minutes
Standard Error 6.7
|
160.1 minutes
Standard Error 16.3
|
|
Gastric Emptying Half-time
Day 3 (n=10, 9)
|
155.6 minutes
Standard Error 9.1
|
155.4 minutes
Standard Error 16.5
|
|
Gastric Emptying Half-time
Day 7 (n=9, 8)
|
154.0 minutes
Standard Error 6.5
|
155.4 minutes
Standard Error 15.0
|
|
Gastric Emptying Half-time
Day 56 (n=9, 6)
|
161.2 minutes
Standard Error 6.2
|
153.4 minutes
Standard Error 16.4
|
SECONDARY outcome
Timeframe: baseline, 8 weeksPopulation: Total number of subjects analyzed varied per time period due to discontinuations, subject and data availability. Subjects analyzed are presented per category as (n=hemin, albumin arms).
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.
Outcome measures
| Measure |
Hemin
n=9 Participants
Panhematin®, Ovation Pharmaceuticals, Deerfield, 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
n=9 Participants
10 iv infusions for 8 weeks
|
|---|---|---|
|
Gastrointestinal Symptoms
8 weeks nausea/vomiting subscore (n=9, 7)
|
1.3 units on a scale
Standard Error 0.4
|
1.3 units on a scale
Standard Error 0.4
|
|
Gastrointestinal Symptoms
Baseline fullness/early satiety subscore (n= 9, 9)
|
3.8 units on a scale
Standard Error 0.3
|
3.4 units on a scale
Standard Error 0.3
|
|
Gastrointestinal Symptoms
8 weeks heartburn/regurgitation subscore (n=9, 7)
|
1.0 units on a scale
Standard Error 0.4
|
0.9 units on a scale
Standard Error 0.5
|
|
Gastrointestinal Symptoms
8 weeks fullness/early satiety subscore (n=9, 7)
|
1.9 units on a scale
Standard Error 0.4
|
2.1 units on a scale
Standard Error 0.5
|
|
Gastrointestinal Symptoms
Baseline bloating subscore (n=9, 9)
|
2.6 units on a scale
Standard Error 0.5
|
3.4 units on a scale
Standard Error 0.4
|
|
Gastrointestinal Symptoms
8 weeks bloating subscore (n=9, 7)
|
1.0 units on a scale
Standard Error 0.3
|
2.4 units on a scale
Standard Error 0.7
|
|
Gastrointestinal Symptoms
Baseline upper abdominal pain score (n= 9, 9)
|
3.7 units on a scale
Standard Error 0.4
|
2.8 units on a scale
Standard Error 0.6
|
|
Gastrointestinal Symptoms
8 weeks upper abdominal pain score (n=9, 7)
|
1.4 units on a scale
Standard Error 0.4
|
1.7 units on a scale
Standard Error 0.6
|
|
Gastrointestinal Symptoms
Baseline lower abdominal pain subscore (n=9, 9)
|
2.6 units on a scale
Standard Error 0.4
|
1.9 units on a scale
Standard Error 0.4
|
|
Gastrointestinal Symptoms
8 weeks lower abdominal pain subscore (n=9, 7)
|
1.3 units on a scale
Standard Error 0.4
|
1.4 units on a scale
Standard Error 0.5
|
|
Gastrointestinal Symptoms
Baseline heartburn/regurgitation subscore (n=9, 9)
|
2.0 units on a scale
Standard Error 0.4
|
1.8 units on a scale
Standard Error 0.4
|
|
Gastrointestinal Symptoms
Baseline FDA NVFP composite subscore (n=9, 9)
|
3.4 units on a scale
Standard Error 0.4
|
3.3 units on a scale
Standard Error 0.2
|
|
Gastrointestinal Symptoms
8 weeks FDA NVFP composite subscore (n=9, 7)
|
1.5 units on a scale
Standard Error 0.4
|
1.7 units on a scale
Standard Error 0.4
|
|
Gastrointestinal Symptoms
Baseline GCSI total score (n= 9, 9)
|
3.1 units on a scale
Standard Error 0.3
|
3.3 units on a scale
Standard Error 0.1
|
|
Gastrointestinal Symptoms
8 weeks GCSI total score (n=9, 7)
|
1.4 units on a scale
Standard Error 0.3
|
1.9 units on a scale
Standard Error 0.5
|
|
Gastrointestinal Symptoms
Baseline nausea/vomiting subscore (n=9, 9)
|
2.9 units on a scale
Standard Error 0.6
|
3.2 units on a scale
Standard Error 0.4
|
SECONDARY outcome
Timeframe: baseline, Day 56Population: Total number of subjects analyzed varied per time period due to discontinuations, subject and data availability. Subjects analyzed are presented per category as (n=hemin, albumin arms).
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.
Outcome measures
| Measure |
Hemin
n=11 Participants
Panhematin®, Ovation Pharmaceuticals, Deerfield, 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
n=9 Participants
10 iv infusions for 8 weeks
|
|---|---|---|
|
Autonomic Functions
CASS vagal score - baseline (n=9, 8)
|
1.6 units on a scale
Standard Error 0.5
|
1.7 units on a scale
Standard Error 1.1
|
|
Autonomic Functions
CASS vagal score - day 56 (n=9, 8)
|
1.2 units on a scale
Standard Error 0.4
|
1.9 units on a scale
Standard Error 0.4
|
|
Autonomic Functions
Cass adrenergic score - baseline (n=5, 6)
|
1.0 units on a scale
Standard Error 0.5
|
1.6 units on a scale
Standard Error 1.3
|
|
Autonomic Functions
Cass adrenergic score - day 56 (n=5, 6)
|
0.6 units on a scale
Standard Error 0.4
|
1.2 units on a scale
Standard Error 0.6
|
SECONDARY outcome
Timeframe: baseline, Day 4, Day 7, Day 56Outcome measures
| Measure |
Hemin
n=11 Participants
Panhematin®, Ovation Pharmaceuticals, Deerfield, 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
n=9 Participants
10 iv infusions for 8 weeks
|
|---|---|---|
|
Serum Creatinine
Baseline
|
1.0 mg/dL
Standard Error 0.1
|
0.7 mg/dL
Standard Error 0.1
|
|
Serum Creatinine
Day 4
|
1.0 mg/dL
Standard Error 0.1
|
0.6 mg/dL
Standard Error 0.1
|
|
Serum Creatinine
Day 7
|
0.9 mg/dL
Standard Error 0.1
|
0.7 mg/dL
Standard Error 0.1
|
|
Serum Creatinine
Day 56
|
0.8 mg/dL
Standard Error 0.1
|
0.7 mg/dL
Standard Error 0.1
|
SECONDARY outcome
Timeframe: baseline, Day 4, Day 7, Day 56Outcome measures
| Measure |
Hemin
n=11 Participants
Panhematin®, Ovation Pharmaceuticals, Deerfield, 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
n=9 Participants
10 iv infusions for 8 weeks
|
|---|---|---|
|
Prothrombin Time
Baseline
|
1.0 International Normalized Ratio (INR)
Standard Error 0.1
|
0.9 International Normalized Ratio (INR)
Standard Error 0.1
|
|
Prothrombin Time
Day 4
|
1.0 International Normalized Ratio (INR)
Standard Error 0.1
|
1.0 International Normalized Ratio (INR)
Standard Error 0.1
|
|
Prothrombin Time
Day 7
|
1.0 International Normalized Ratio (INR)
Standard Error 0.1
|
1.0 International Normalized Ratio (INR)
Standard Error 0.1
|
|
Prothrombin Time
Day 56
|
1.0 International Normalized Ratio (INR)
Standard Error 0.1
|
1.0 International Normalized Ratio (INR)
Standard Error 0.1
|
SECONDARY outcome
Timeframe: baseline, Day 4, Day 7, Day 56Outcome measures
| Measure |
Hemin
n=11 Participants
Panhematin®, Ovation Pharmaceuticals, Deerfield, 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
n=9 Participants
10 iv infusions for 8 weeks
|
|---|---|---|
|
Activated Partial Thromboplastin Time (APTT)
Baseline
|
32 Seconds
Standard Error 1.8
|
32 Seconds
Standard Error 0.9
|
|
Activated Partial Thromboplastin Time (APTT)
Day 4
|
33 Seconds
Standard Error 1.0
|
31 Seconds
Standard Error 1.5
|
|
Activated Partial Thromboplastin Time (APTT)
Day 7
|
30 Seconds
Standard Error 1.3
|
31 Seconds
Standard Error 1.4
|
|
Activated Partial Thromboplastin Time (APTT)
Day 56
|
30 Seconds
Standard Error 1.2
|
32 Seconds
Standard Error 1.3
|
SECONDARY outcome
Timeframe: baseline, Day 4, Day 7, Day 56Measured by complete blood count
Outcome measures
| Measure |
Hemin
n=11 Participants
Panhematin®, Ovation Pharmaceuticals, Deerfield, 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
n=9 Participants
10 iv infusions for 8 weeks
|
|---|---|---|
|
Hemoglobin
Baseline
|
12.1 g/dL
Standard Error 0.4
|
12.4 g/dL
Standard Error 0.5
|
|
Hemoglobin
Day 4
|
11.5 g/dL
Standard Error 0.5
|
11.5 g/dL
Standard Error 0.5
|
|
Hemoglobin
Day 7
|
11.6 g/dL
Standard Error 0.6
|
11.2 g/dL
Standard Error 0.4
|
|
Hemoglobin
Day 56
|
11.3 g/dL
Standard Error 0.6
|
11.2 g/dL
Standard Error 0.3
|
SECONDARY outcome
Timeframe: baseline, Day 4, Day 7, Day 56Measured by complete blood count
Outcome measures
| Measure |
Hemin
n=11 Participants
Panhematin®, Ovation Pharmaceuticals, Deerfield, 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
n=9 Participants
10 iv infusions for 8 weeks
|
|---|---|---|
|
Erythrocyte Count
Baseline
|
4.1 number x 10^12 erythrocytes/L
Standard Error 0.1
|
4.4 number x 10^12 erythrocytes/L
Standard Error 0.1
|
|
Erythrocyte Count
Day 4
|
4.0 number x 10^12 erythrocytes/L
Standard Error 0.1
|
4.1 number x 10^12 erythrocytes/L
Standard Error 0.1
|
|
Erythrocyte Count
Day 7
|
4.0 number x 10^12 erythrocytes/L
Standard Error 0.2
|
4.0 number x 10^12 erythrocytes/L
Standard Error 0.1
|
|
Erythrocyte Count
Day 56
|
4.0 number x 10^12 erythrocytes/L
Standard Error 0.2
|
4.0 number x 10^12 erythrocytes/L
Standard Error 0.1
|
SECONDARY outcome
Timeframe: baseline, Day 4, Day 7, Day 56Measured by complete blood count
Outcome measures
| Measure |
Hemin
n=11 Participants
Panhematin®, Ovation Pharmaceuticals, Deerfield, 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
n=9 Participants
10 iv infusions for 8 weeks
|
|---|---|---|
|
Leukocyte and Platelet Counts
Leukocytes Baseline
|
7.0 number x 10^9 cells/L
Standard Error 0.6
|
6.0 number x 10^9 cells/L
Standard Error 0.5
|
|
Leukocyte and Platelet Counts
Leukocytes Day 4
|
7.0 number x 10^9 cells/L
Standard Error 0.5
|
6.2 number x 10^9 cells/L
Standard Error 0.6
|
|
Leukocyte and Platelet Counts
Leukocytes Day 7
|
7.2 number x 10^9 cells/L
Standard Error 0.6
|
6.8 number x 10^9 cells/L
Standard Error 1.2
|
|
Leukocyte and Platelet Counts
Leukocytes Day 56
|
7.3 number x 10^9 cells/L
Standard Error 0.5
|
6.5 number x 10^9 cells/L
Standard Error 0.8
|
|
Leukocyte and Platelet Counts
Platelets Baseline
|
248 number x 10^9 cells/L
Standard Error 18
|
266 number x 10^9 cells/L
Standard Error 26
|
|
Leukocyte and Platelet Counts
Platelets Day 7
|
201 number x 10^9 cells/L
Standard Error 15
|
248 number x 10^9 cells/L
Standard Error 26
|
|
Leukocyte and Platelet Counts
Platelets Day 56
|
212 number x 10^9 cells/L
Standard Error 12
|
251 number x 10^9 cells/L
Standard Error 41
|
|
Leukocyte and Platelet Counts
Platelets Day 4
|
194 number x 10^9 cells/L
Standard Error 14
|
246 number x 10^9 cells/L
Standard Error 21
|
Adverse Events
Hemin
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Albumin
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Hemin
n=11 participants at risk
Panhematin®, Ovation Pharmaceuticals, Deerfield, 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
n=9 participants at risk
10 iv infusions for 8 weeks
|
|---|---|---|
|
General disorders
Headache
|
18.2%
2/11 • Number of events 2 • 8 weeks
|
33.3%
3/9 • Number of events 3 • 8 weeks
|
|
Gastrointestinal disorders
Nausea
|
9.1%
1/11 • Number of events 1 • 8 weeks
|
33.3%
3/9 • Number of events 3 • 8 weeks
|
|
General disorders
Dizziness or light headedness
|
18.2%
2/11 • Number of events 2 • 8 weeks
|
0.00%
0/9 • 8 weeks
|
|
Skin and subcutaneous tissue disorders
Maculopapular rash
|
0.00%
0/11 • 8 weeks
|
11.1%
1/9 • Number of events 1 • 8 weeks
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place