search
Back to results

Hydroxychloroquine and Metabolic Outcomes in Patients Undergoing TPAIT

Primary Purpose

Chronic Pancreatitis, Insulin Dependent Diabetes

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Hydroxychloroquine
Placebo
Sponsored by
The Cleveland Clinic
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Pancreatitis focused on measuring Pancreatectomy, Autologous Islet Transplantation, Pancreatitis, Diabetes, Hydroxychloroquine

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Clinically confirmed diagnosis of chronic pancreatitis (CP)
  • Intractable abdominal pain
  • History of failed operation(s) for CP
  • Recurrent acute pancreatitis
  • HbA1c <8.0%
  • Sustained alcohol remission
  • Chronic narcotic use

Exclusion Criteria:

  • Insulin dependence
  • Pancreatic carcinoma
  • Pancreatic mass suspicious for carcinoma
  • Cirrhosis
  • Portal hypertension
  • Continued alcohol abuse
  • Manufacturer's product label-contraindicated use of HCQ
  • History of retinopathy
  • Actual weight at enrollment <40 Kg

Sites / Locations

  • Cleveland Clinic

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Hydroxychloroquine

Placebo

Arm Description

Administered pre-transplant through 3 months after surgery.

Placebo treatment following the same schedule as Arm 1 (i.e. Hydroxychloroquine).

Outcomes

Primary Outcome Measures

Quotient of Stimulated C-peptide/Glucose Level Normalized for IEQ/Kg Infused in Response to MMTT
HCQ-treated compared to placebo arm. This outcome measure was reported in Mean and Standard deviation looking at C peptide/glucose secretion at 90 mins during mixed meal test adjusted for IEG/Kg (islet cell equivalency) infused to the patient.

Secondary Outcome Measures

C-peptide AUC Response to MMTT
HCQ-treated compared to placebo arm. We used a standard, 5 hour Mixed meal tolerance test (MMT). Blood draws were taken every 15 mins for the first hours, then every 30 mins the second hour, then hourly until completion.
Ratio of C-peptide AUC to Glucose AUC in Response to MMTT Adjusted for Infused Islet Cell Mass
C-peptide, ng/mL/min/IEQ/kg iAUC post-MMTT. Our measurement can be reported in area under the curve for C-peptide normalized for glucose values as well as Islet cell mass infused to the patient in order to compare placebo vs intervention arms.

Full Information

First Posted
September 13, 2017
Last Updated
April 6, 2022
Sponsor
The Cleveland Clinic
Collaborators
Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute), Stanford University
search

1. Study Identification

Unique Protocol Identification Number
NCT03283566
Brief Title
Hydroxychloroquine and Metabolic Outcomes in Patients Undergoing TPAIT
Official Title
Hydroxychloroquine and Metabolic Outcomes in Patients Undergoing Total Pancreatectomy and Autologous Islet Transplantation: A Clinical, Molecular, and Genomic Study
Study Type
Interventional

2. Study Status

Record Verification Date
April 2022
Overall Recruitment Status
Completed
Study Start Date
October 3, 2017 (Actual)
Primary Completion Date
May 31, 2020 (Actual)
Study Completion Date
May 31, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
The Cleveland Clinic
Collaborators
Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute), Stanford University

4. Oversight

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.
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This will be a pilot, 12-month phase II, open label, randomized, two-arm, single-blinded, placebo-controlled, parallel clinical trial of individuals undergoing TPAIT (Total Pancreatectomy and Autologous Islet Transplantation) for treatment of chronic pancreatitis (CP). The two study arms consist of HCQ-treated (Hydroxychloroquine) and placebo-treated individuals. The purpose of this study is to investigate the effects of HCQ administration compared to placebo on islet cell function post-autologous transplantation.
Detailed Description
A compelling level of evidence exists on the effects of the innate immunity-driven inflammation on the decline of functional beta cell mass in the autologous transplant setting. The investigators hypothesize that HCQ administration during the peri-transplant period will preserve islet mass and improve islet cell function in TPAIT by reducing inflammation. The investigators specifically aim to demonstrate a higher stimulated C-peptide level as well as greater glucose control in response to mixed meal tolerance testing (MMTT) at 6 and 12 months following TPAIT in patients treated with HCQ compared to placebo. A better response in the HCQ arm suggests improved islet survival and metabolic performance, potentially facilitating higher rates of insulin independence. HCQ administration: Arm 1 (n=5): Subjects will receive a pre-transplant HCQ 200 mg daily dose 30 days prior TPAIT followed by HCQ use for an additional 3 months post-surgery. Arm 2 (n=5) subjects will receive placebo treatment following the same schedule as in Arm 1. Exploratory mechanistic studies: All subjects will undergo a MMTT to assess islet cell function at 6 and 12 months following TPAIT (in addition to MMTT pre-surgery performed as standard of care, and whose results will be used for pre-randomization in this pilot). Baseline metabolic tests obtained too early after surgery may not be indicative of islet function, due to insulin supporting therapy administered for several weeks after transplantation. Also, compelling data indicate that stabilization of islet function may require up to 1 year to occur. Blood glucose and C-peptide serum levels will be measured in peripheral blood samples immediately prior and subsequent to MMTT. The research coordinator will contact the subjects at 3, 6 and 12 months for interview on the course of follow up and will assist in scheduling the 6 and 12-month appointments for MMTT. Mitochondrial Function and Metabolic Outcomes in TPAIT: Mitochondrial efficiency is important in the setting of TPAIT, where increase in metabolic demand and decrease in oxygenation have been established. The investigators will assess mitochondrial efficiency by measuring rates of mitochondrial respiration and glycolysis. These measures will be obtained on islets procured for donation and after islet isolation. Small amounts of digest left after islet isolation, that would normally be discarded, will be used for this portion of the study. The islets from the digest will be collected and will undergo extracellular efflux analysis through the Seahorse XF analyzer for mitochondrial function assessment. Commercially available normal human islet cells for experiments will be used as control. Controls will be compared simultaneously with islets isolated from study subjects. Genome-wide Gene Expression in TPAIT Patients: On the genomic level, several genetic pathways have been implicated in islet cell function and survival. The genetic profiles of islet cells from CP patients undergoing TPAIT have not been evaluated yet. The investigators aim to build an RNA-gene sequence database for islet cells of CP patients undergoing TPAIT, specifically targeting genes previously identified as key players in islet function. Small amounts of digest from the procedure used for isolating islets, and what remains in the circuit after the isolation process is complete, that would normally be discarded, will also be used for islet gene expression assessment.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Pancreatitis, Insulin Dependent Diabetes
Keywords
Pancreatectomy, Autologous Islet Transplantation, Pancreatitis, Diabetes, Hydroxychloroquine

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
open label, randomized, two-arm, single-blinded, placebo-controlled, parallel
Masking
ParticipantInvestigatorOutcomes Assessor
Masking Description
The study will be single-blinded. The PI, biostatistician who will analyze the data, consultants, and technicians running assays will be blinded to the study arm into which the subjects have been randomized. An alphanumeric identifier that refers to the study subject without any indicators of study arm allocation will be used. Only the surgeons and the research coordinator, but not the personnel conducting the metabolic studies, will be un-blinded as to the study arm randomization.
Allocation
Randomized
Enrollment
9 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Hydroxychloroquine
Arm Type
Active Comparator
Arm Description
Administered pre-transplant through 3 months after surgery.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo treatment following the same schedule as Arm 1 (i.e. Hydroxychloroquine).
Intervention Type
Drug
Intervention Name(s)
Hydroxychloroquine
Other Intervention Name(s)
Plaquenil
Intervention Description
Subjects will receive a pre-transplant 200 mg daily dose of HCQ 30 days before TPAIT and will continue on the drug for 3 months after surgery.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Subjects will receive a pre-transplant placebo 30 days before TPAIT and will continue on the placebo for 3 months after surgery.
Primary Outcome Measure Information:
Title
Quotient of Stimulated C-peptide/Glucose Level Normalized for IEQ/Kg Infused in Response to MMTT
Description
HCQ-treated compared to placebo arm. This outcome measure was reported in Mean and Standard deviation looking at C peptide/glucose secretion at 90 mins during mixed meal test adjusted for IEG/Kg (islet cell equivalency) infused to the patient.
Time Frame
12 months
Secondary Outcome Measure Information:
Title
C-peptide AUC Response to MMTT
Description
HCQ-treated compared to placebo arm. We used a standard, 5 hour Mixed meal tolerance test (MMT). Blood draws were taken every 15 mins for the first hours, then every 30 mins the second hour, then hourly until completion.
Time Frame
12 months
Title
Ratio of C-peptide AUC to Glucose AUC in Response to MMTT Adjusted for Infused Islet Cell Mass
Description
C-peptide, ng/mL/min/IEQ/kg iAUC post-MMTT. Our measurement can be reported in area under the curve for C-peptide normalized for glucose values as well as Islet cell mass infused to the patient in order to compare placebo vs intervention arms.
Time Frame
12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Clinically confirmed diagnosis of chronic pancreatitis (CP) Intractable abdominal pain History of failed operation(s) for CP Recurrent acute pancreatitis HbA1c <8.0% Sustained alcohol remission Chronic narcotic use Exclusion Criteria: Insulin dependence Pancreatic carcinoma Pancreatic mass suspicious for carcinoma Cirrhosis Portal hypertension Continued alcohol abuse Manufacturer's product label-contraindicated use of HCQ History of retinopathy Actual weight at enrollment <40 Kg
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Betul Hatipoglu, MD
Organizational Affiliation
Staff
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Hydroxychloroquine and Metabolic Outcomes in Patients Undergoing TPAIT

We'll reach out to this number within 24 hrs