Skin Blood Flow Response to Insulin Iontophoresis in Pressure Ulcers of SCI

Insulin Sensitivity in the Peri-Wound Microcirculation of Pressure Ulcers in SCI

Pressure ulcers (PU) are skin breakdowns that often form after blood flow in the skin is reduced from prolonged and repeated exposure to externally applied forces. As many as 85% of individuals with a spinal cord injury (SCI) report the occurrence of at least 1 PU since being injured. Despite the increasing attention and emphasis on prevention, PUs still represent a major health risk for persons with SCI. Among the numerous potential physical risk factors identified for the development of a PU were several conditions that have a significant negative effect on skin blood flow. In addition, improper management of blood sugar is a major risk factor for PU development and it impedes healing. It would appear that hormones (i.e., chemical signals in the blood) associated with how the body uses sugar that target the blood vessels may play an important role in the development and formation of a PU. In persons with SCI, skin blood flow responses to insulin (i.e., a hormone that helps the body use sugar and also relaxes the blood vessels allowing blood flow to increase) in the lower extremity were shown to be much lower than healthy individuals.

The proposed study in up to 30 individuals with chronic SCI and a difficult-to-heal pelvic region PU has 2 phases: (1) a 4-week "observation" phase [if the PU does not heal appropriately (determined by digital photos and software computation), and the subject is found to be insulin resistant then they will progress to the next phase of the study] and (2) an 8-week "treatment" phase. All participants will continue to receive the standard wound care throughout the observation and treatment phases. If the surface area of the PU does not decrease by more than 30% during the 4-week observation phase, the participant will be eligible to enter the 8-week treatment phase, in which they will be randomly assigned to receive active drug (e.g., pioglitazone) or placebo. The participants will have four study visits in which the following will be acquired: digital image of the wound to monitor wound surface area, skin blood flow measurements of the peri-wound area, and blood tests to monitor liver function, kidney function, blood sugar (hemoglobin A1C, insulin, glucose), nutritional status (albumin and pre-albumin), a complete blood count with differential, and makers of inflammation. Weekly monitoring of symptoms and participant experiences will be closely monitored.

Study Overview

• Status: Withdrawn
• Conditions: Spinal Cord Injury; Pressure Ulcers
• Intervention / Treatment: Drug: Pioglitazone; Drug: Placebo

Detailed Description

Pressure ulcers (PU) are skin breakdowns that often form after blood flow in the skin is reduced from prolonged and repeated exposure to externally applied forces. As many as 85% of individuals with a spinal cord injury (SCI) report the occurrence of at least 1 PU since being injured. Despite the increasing attention and emphasis on prevention strategies, PUs still represent a major risk for morbidity in persons with SCI. Among the numerous potential physical risk factors identified for the development of a PU were several conditions that have a significant adverse influences on skin blood flow. In addition, poor glycemic control is a major risk factor for PU development and it impedes healing. Thus, it would appear that vasoactive hormones associated with carbohydrate metabolism that target the endothelium may play an important role in the development and formation of a PU. In persons with SCI, skin blood flow responses to insulin in the lower extremity were shown to be much lower than healthy individuals despite no clinical signs of insulin resistance. In the skin next to a PU, the current proposal will determine if a once-daily treatment with pioglitazone for 8 weeks improves skin blood flow after insulin by iontophoresis.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • Bronx, New York, United States, 10468
      • James J. Peters VA Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female, age 18 to 79;
2. Chronic (e.g., duration of injury at least 6 months), stable SCI (regardless of level of neurological lesion);
3. American Spinal Injury Association Impairment Scale (AIS) designation of A, B or C; and
4. At least one Stage III or IV PU in the pelvic region (e.g., ischial, trochanteric, perineal, and sacral regions) that has not shown signs of healing for a period of at least 1 month.
5. Hemoglobin A1C <7.0%

Exclusion Criteria:

1. Persons who are candidates for or elect to have reconstructive flap surgery of the PU;
2. Hemoglobin A1C ≥7.0%
3. Psychopathology (documentation in the medical record or history of self-abusive behavior specific to PU healing which may or may not include major or minor psychiatric illness (that may conflict with the study objectives;
4. Previously diagnosed active malignant disease;
5. Suspicion of skin cancer at the PU site (i.e., clinical evaluation is currently on-going);
6. Life expectancy less than 12 months;
7. Nephrosis, hemodialysis or chronic ambulatory peritoneal dialysis therapy;
8. Acute illness or systemic infection (including MRSA);
9. Current pharmacological treatment for diabetes mellitus or insulin resistance with exogenous insulin (or its synthetic dialogues), insulin-sensitizing agents, or agents that alter pancreatic secretion of insulin;
10. Current pharmacological treatment with sympathomimetic agents demonstrating direct vascular actions or indirect implications (e.g., alpha-1 agonists, cholinesterase inhibitors, norepinephrine, calcium channel blockers, angiotensin converting enzymes);
11. Moderate to high dose glucocorticoid administrations (i.e., ≥ 40 mg prednisone or equivalent steroid dose) within the past 3 months;
12. Atherosclerosis, congestive heart failure, or recent history of myocardial infarction (<90 months);
13. Previous diagnosis of diabetes mellitus or insulin resistance;
14. Diminished mental capacity;
15. Inability or unwillingness of subject to provide informed consent; or
16. Pregnancy or women who may become pregnant during the course of the study, or those who are nursing.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pioglitazone; Subjects will receive 8 weeks of daily pioglitazone (30mg/day).	Drug: Pioglitazone; 8 weeks of daily pioglitazone (30 mg/d).
Placebo Comparator: Placebo; Subjects will receive 8 weeks of daily placebo capsules.	Drug: Placebo; 8 weeks of daily placebo capsules.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Skin Perfusion Response to Insulin Administered by Iontophoresis to the Cutaneous Peri-Wound region of a Chronic Region Pressure Ulcer before and after treatment with Pioglitazone	To determine the perfusion response to insulin administered by iontophoresis to the cutaneous peri-wound region of a chronic pelvic region pressure ulcer before and after treatment with pioglitazone (30 mg/d x 8 weeks).	Before and After 8 Week Treatment with Pioglitazone

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Association between the therapeutic effects of pioglitazone on the homeostatic model assessment of insulin resistance (HOMA-IR) and cutaneous peri-wound perfusion response to transdermal insulin administration.	To determine the association between the therapeutic effects of pioglitazone on the homeostatic model assessment of insulin resistance (HOMA-IR) and cutaneous peri-wound perfusion response to transdermal insulin administration.	Before and After 8 Week Treatment with Pioglitazone

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reliability of laser speckle contrast analysis imaging to detect meaningful interventional change in cutaneous peri-wound perfusion to pioglitazone treatment.	To determine the reliability of laser speckle contrast analysis imaging to detect meaningful interventional change in cutaneous peri-wound perfusion to pioglitazone treatment.	Before and After 8 Week Treatment with Pioglitazone

Collaborators and Investigators

• Sponsor: James J. Peters Veterans Affairs Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2017
• Primary Completion (Actual): April 1, 2018
• Study Completion (Actual): April 1, 2018

Study Registration Dates

• First Submitted: October 22, 2015
• First Submitted That Met QC Criteria: October 22, 2015
• First Posted (Estimate): October 23, 2015

Study Record Updates

• Last Update Posted (Actual): August 8, 2018
• Last Update Submitted That Met QC Criteria: August 6, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Central Nervous System Diseases; Nervous System Diseases; Skin Diseases; Wounds and Injuries; Skin Ulcer; Trauma, Nervous System; Spinal Cord Diseases; Ulcer; Spinal Cord Injuries; Pressure Ulcer; Hypoglycemic Agents; Physiological Effects of Drugs; Pioglitazone
• Other Study ID Numbers: LAF-15-040

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No