Nitrite Infusion in Islet Cell Transplantation

• Sponsor: University of Alabama at Birmingham (Other)
• Overall Status: Terminated
• CT.gov ID: NCT03544242
• Collaborator: (none)
• Enrollment: 4
• Location: 1
• Arms: 3
• Actual Duration (Months): 25.7
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This study seeks to investigate the effects of administering nitrite to pancreatic islet cells that have been removed from a patient for autotransplantation.

Condition or Disease	Intervention/Treatment	Phase
Diabetes	Other: Control; Drug: Pre-Isolation Infusion; Drug: Post-Isolation Infusion	Phase 2

Detailed Description

Patients diagnosed with chronic pancreatitis or recurrent acute pancreatitis may acquire insulin-dependent diabetes due to islet cell destruction. Therefore, islet cell autotransplantation is the optimal therapeutic approach for many of these patients. Islet cell autotransplantation is typically done by excision of the pancreas, followed by isolation of the islet cells and then infusion of these cells into the sinusoids of the liver. Isolation of the islet cells occurs in an ischemic and hypoxic environment, resulting in ischemia reperfusion (IR) injury and destruction of islet cells following infusion into the sinusoids. Hence, strategies to prevent IR injury and subsequent islet cell destruction, such as the administration of inhaled nitric oxide (NO) or sodium nitrite (NaNO2) could enhance islet cell survival following reperfusion, also decreasing long-term insulin requirement. The purpose of this study is to determine if NO administered by infusion in patients undergoing islet cell auto transplantation, will inhibit islet cell destruction, increase diabetes cure rate (decrease the amount of and/or the need for long-term insulin requirement), decrease the ischemic injury (reduces the injury to the islet cells from a decrease in oxygen levels during procurement of the islet cells) during islet cell procurement, and decrease IR injury following islet cell infusion. The primary endpoints of the study are exogenous insulin use, HgbA1c levels post-operatively, and blood glucose levels.

Study Design

• Study Type: Interventional
• Actual Enrollment: 4 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Care Provider)
• Primary Purpose: Treatment
• Official Title: Nitrite Infusion in Islet Cell Transplantation: Test of Clinical Efficacy and Determination of Cytoprotective Mechanisms
• Actual Study Start Date: May 7, 2017
• Actual Primary Completion Date: Jun 27, 2019
• Actual Study Completion Date: Jun 27, 2019

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Control group	Other: Control; A saline infusion will be administered during the pre-isolation and post-isolation phases.
Experimental: Pre-Isolation Infusion	Drug: Pre-Isolation Infusion; A nitrite infusion will be administered during the pre-isolation phase and a saline infusion will be administered during the post-isolation phase.
Experimental: Post-Isolation Infusion	Drug: Post-Isolation Infusion; A saline infusion will be administered during the pre-isolation phase and a nitrite infusion will be administered during the reperfusion phase.

Outcome Measures

Primary Outcome Measures

1. Prior to Infusion Blood Glucose Serum Levels [Between the time of induction and the time immediately prior to infusion of either nitrite or saline]

   Blood serum glucose levels will be measured from a blood sample of the amount of 3-5 cc.

2. Pre-islet Cell Infusion Blood Serum Glucose Levels [Five minutes prior to the infusion of islet cells]

   Blood serum glucose levels will be measured from a blood sample of the amount of 3-5 cc.

3. 20 Minutes After Islet Cells Blood Serum Glucose Levels [20 minutes after the infusion of Islet Cells]

   Blood serum glucose levels will be measured from a blood sample of the amount of 3-5 cc.

4. 40 Minutes After Islet Cells Blood Serum Glucose Levels [40 minutes after the infusion of Islet Cells]

   Blood serum glucose levels will be measured from a blood sample of the amount of 3-5 cc.

5. 24 Hours Post Operative Blood Samples Serum Glucose Levels [24 hours post operatively]

   Blood serum glucose levels will be measured from a blood sample of the amount of 3-5 cc.

6. 48 Hours Post Operative Blood Samples Serum Glucose Levels [48 hours post operatively]

   Blood serum glucose levels will be measured from a blood sample of the amount of 3-5 cc.

7. 72 Hours Post Operative Blood Samples Serum Glucose Levels [72 hours post operatively]

   Blood serum glucose levels will be measured from a blood sample of the amount of 3-5 cc.

8. 96 Hours Post Operative Blood Samples Serum Glucose Levels [96 hours post operatively]

   Blood serum glucose levels will be measured from a blood sample of the amount of 3-5 cc.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients greater than or equal to 18 years of age

• Scheduled to undergo Islet Cell auto-transplantation by Dr. Jared White or Dr. Bart Rose

• Subjects who can provide informed written consent and are willing to do so

Exclusion Criteria:

-Any patient with liver disease or unsuitable for surgery (as determined by the surgeon)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294

Sponsors and Collaborators

• University of Alabama at Birmingham

Investigators

• Principal Investigator: Blair Smith, MD, University of Alabama at Birmingham

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jul 17, 2018

More Information

Publications

None provided.

• Responsible Party: Blair Smith, Principal Investigator, University of Alabama at Birmingham
• ClinicalTrials.gov Identifier: NCT03544242
• Other Study ID Numbers: IRB-160901003
• First Posted: Jun 1, 2018
• Last Update Posted: Oct 29, 2020
• Last Verified: Oct 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Keywords provided by Blair Smith, Principal Investigator, University of Alabama at Birmingham: Diabetes; Insulin Resistance; Nitrite; Pancreatic islet cells; Autotransplantation; Ischemia reperfusion injury; Mitigation; Cure; Nitric oxide; Sodium nitrite; Islet cell; Survival; Pancreas; Liver

Study Results

Participant Flow

Arm/Group Title	Control Group	Pre-Isolation Infusion	Post-Isolation Infusion
Arm/Group Description	Control: A saline infusion will be administered during the pre-isolation and post-isolation phases.	Pre-Isolation Infusion: A nitrite infusion will be administered during the pre-isolation phase and a saline infusion will be administered during the post-isolation phase.	Post-Isolation Infusion: A saline infusion will be administered during the pre-isolation phase and a nitrite infusion will be administered during the reperfusion phase.
Period Title: Overall Study
STARTED	1	1	2
COMPLETED	1	1	2
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	Control Group	Pre-Isolation Infusion	Post-Isolation Infusion	Total
Arm/Group Description	Control: A saline infusion will be administered during the pre-isolation and post-isolation phases.	Pre-Isolation Infusion: A nitrite infusion will be administered during the pre-isolation phase and a saline infusion will be administered during the post-isolation phase.	Post-Isolation Infusion: A saline infusion will be administered during the pre-isolation phase and a nitrite infusion will be administered during the reperfusion phase.	Total of all reporting groups
Overall Participants	1	1	2	4
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	1 100%	1 100%	2 100%	4 100%
>=65 years	0 0%	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	1 100%	1 100%	1 50%	3 75%
Male	0 0%	0 0%	1 50%	1 25%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%
White	1 100%	1 100%	2 100%	4 100%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	1 100%	1 100%	2 100%	4 100%

Outcome Measures

1. Primary Outcome

Title	Prior to Infusion Blood Glucose Serum Levels
Description	Blood serum glucose levels will be measured from a blood sample of the amount of 3-5 cc.
Time Frame	Between the time of induction and the time immediately prior to infusion of either nitrite or saline

Outcome Measure Data

Analysis Population Description

The study did not reach sufficient enrollment power for statistical analysis.

Arm/Group Title	Control Group	Pre-Isolation Infusion	Post-Isolation Infusion
Arm/Group Description	Control: A saline infusion will be administered during the pre-isolation and post-isolation phases.	Pre-Isolation Infusion: A nitrite infusion will be administered during the pre-isolation phase and a saline infusion will be administered during the post-isolation phase.	Post-Isolation Infusion: A saline infusion will be administered during the pre-isolation phase and a nitrite infusion will be administered during the reperfusion phase.
Measure Participants	0	0	0

2. Primary Outcome

Title	Pre-islet Cell Infusion Blood Serum Glucose Levels
Description	Blood serum glucose levels will be measured from a blood sample of the amount of 3-5 cc.
Time Frame	Five minutes prior to the infusion of islet cells

Outcome Measure Data

Analysis Population Description

The study did not reach sufficient enrollment power for statistical analysis.

Arm/Group Title	Control Group	Pre-Isolation Infusion	Post-Isolation Infusion
Arm/Group Description	Control: A saline infusion will be administered during the pre-isolation and post-isolation phases.	Pre-Isolation Infusion: A nitrite infusion will be administered during the pre-isolation phase and a saline infusion will be administered during the post-isolation phase.	Post-Isolation Infusion: A saline infusion will be administered during the pre-isolation phase and a nitrite infusion will be administered during the reperfusion phase.
Measure Participants	0	0	0

3. Primary Outcome

Title	20 Minutes After Islet Cells Blood Serum Glucose Levels
Description	Blood serum glucose levels will be measured from a blood sample of the amount of 3-5 cc.
Time Frame	20 minutes after the infusion of Islet Cells

Outcome Measure Data

Analysis Population Description

The study did not reach sufficient enrollment power for statistical analysis.

Arm/Group Title	Control Group	Pre-Isolation Infusion	Post-Isolation Infusion
Arm/Group Description	Control: A saline infusion will be administered during the pre-isolation and post-isolation phases.	Pre-Isolation Infusion: A nitrite infusion will be administered during the pre-isolation phase and a saline infusion will be administered during the post-isolation phase.	Post-Isolation Infusion: A saline infusion will be administered during the pre-isolation phase and a nitrite infusion will be administered during the reperfusion phase.
Measure Participants	0	0	0

4. Primary Outcome

Title	40 Minutes After Islet Cells Blood Serum Glucose Levels
Description	Blood serum glucose levels will be measured from a blood sample of the amount of 3-5 cc.
Time Frame	40 minutes after the infusion of Islet Cells

Outcome Measure Data

Analysis Population Description

The study did not reach sufficient enrollment power for statistical analysis.

Arm/Group Title	Control Group	Pre-Isolation Infusion	Post-Isolation Infusion
Arm/Group Description	Control: A saline infusion will be administered during the pre-isolation and post-isolation phases.	Pre-Isolation Infusion: A nitrite infusion will be administered during the pre-isolation phase and a saline infusion will be administered during the post-isolation phase.	Post-Isolation Infusion: A saline infusion will be administered during the pre-isolation phase and a nitrite infusion will be administered during the reperfusion phase.
Measure Participants	0	0	0

5. Primary Outcome

Title	24 Hours Post Operative Blood Samples Serum Glucose Levels
Description	Blood serum glucose levels will be measured from a blood sample of the amount of 3-5 cc.
Time Frame	24 hours post operatively

Outcome Measure Data

Analysis Population Description

The study did not reach sufficient enrollment power for statistical analysis.

Arm/Group Title	Control Group	Pre-Isolation Infusion	Post-Isolation Infusion
Arm/Group Description	Control: A saline infusion will be administered during the pre-isolation and post-isolation phases.	Pre-Isolation Infusion: A nitrite infusion will be administered during the pre-isolation phase and a saline infusion will be administered during the post-isolation phase.	Post-Isolation Infusion: A saline infusion will be administered during the pre-isolation phase and a nitrite infusion will be administered during the reperfusion phase.
Measure Participants	0	0	0

6. Primary Outcome

Title	48 Hours Post Operative Blood Samples Serum Glucose Levels
Description	Blood serum glucose levels will be measured from a blood sample of the amount of 3-5 cc.
Time Frame	48 hours post operatively

Outcome Measure Data

Analysis Population Description

The study did not reach sufficient enrollment power for statistical analysis.

Arm/Group Title	Control Group	Pre-Isolation Infusion	Post-Isolation Infusion
Arm/Group Description	Control: A saline infusion will be administered during the pre-isolation and post-isolation phases.	Pre-Isolation Infusion: A nitrite infusion will be administered during the pre-isolation phase and a saline infusion will be administered during the post-isolation phase.	Post-Isolation Infusion: A saline infusion will be administered during the pre-isolation phase and a nitrite infusion will be administered during the reperfusion phase.
Measure Participants	0	0	0

7. Primary Outcome

Title	72 Hours Post Operative Blood Samples Serum Glucose Levels
Description	Blood serum glucose levels will be measured from a blood sample of the amount of 3-5 cc.
Time Frame	72 hours post operatively

Outcome Measure Data

Analysis Population Description

The study did not reach sufficient enrollment power for statistical analysis.

Arm/Group Title	Control Group	Pre-Isolation Infusion	Post-Isolation Infusion
Arm/Group Description	Control: A saline infusion will be administered during the pre-isolation and post-isolation phases.	Pre-Isolation Infusion: A nitrite infusion will be administered during the pre-isolation phase and a saline infusion will be administered during the post-isolation phase.	Post-Isolation Infusion: A saline infusion will be administered during the pre-isolation phase and a nitrite infusion will be administered during the reperfusion phase.
Measure Participants	0	0	0

8. Primary Outcome

Title	96 Hours Post Operative Blood Samples Serum Glucose Levels
Description	Blood serum glucose levels will be measured from a blood sample of the amount of 3-5 cc.
Time Frame	96 hours post operatively

Outcome Measure Data

Analysis Population Description

The study did not reach sufficient enrollment power for statistical analysis.

Arm/Group Title	Control Group	Pre-Isolation Infusion	Post-Isolation Infusion
Arm/Group Description	Control: A saline infusion will be administered during the pre-isolation and post-isolation phases.	Pre-Isolation Infusion: A nitrite infusion will be administered during the pre-isolation phase and a saline infusion will be administered during the post-isolation phase.	Post-Isolation Infusion: A saline infusion will be administered during the pre-isolation phase and a nitrite infusion will be administered during the reperfusion phase.
Measure Participants	0	0	0

Adverse Events

Time Frame	from baseline through 24 months post-operatively
Adverse Event Reporting Description	Patients were evaluated for adverse events during appointments.
Arm/Group Title	Control Group		Pre-Isolation Infusion		Post-Isolation Infusion
Arm/Group Description	Control: A saline infusion will be administered during the pre-isolation and post-isolation phases.		Pre-Isolation Infusion: A nitrite infusion will be administered during the pre-isolation phase and a saline infusion will be administered during the post-isolation phase.		Post-Isolation Infusion: A saline infusion will be administered during the pre-isolation phase and a nitrite infusion will be administered during the reperfusion phase.
All Cause Mortality
	Control Group		Pre-Isolation Infusion		Post-Isolation Infusion
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/1 (0%)		0/2 (0%)
Serious Adverse Events
	Control Group		Pre-Isolation Infusion		Post-Isolation Infusion
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/1 (0%)		0/2 (0%)
Other (Not Including Serious) Adverse Events
	Control Group		Pre-Isolation Infusion		Post-Isolation Infusion
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/1 (0%)		0/2 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.