Ignite Creation Date:
2024-05-06 @ 7:46 PM
Last Modification Date:
2024-10-26 @ 3:13 PM
Study NCT ID:
NCT06124586
Status:
RECRUITING
Last Update Posted:
2024-02-16
First Post:
2023-08-21
Brief Title:
Early Percutaneous Transluminal Angioplasty in Diabetic Foot Syndrome PTA-DFS
Sponsor:
Heinrich-Heine University Duesseldorf
Organization:
Heinrich-Heine University Duesseldorf
Study Overview
Official Title:
Role of Percutaneous Transluminal Angioplasty for Wound Healing and Dynamics of the Microbial Community in Patients With Type 2 Diabetes and Diabetic Foot Syndrome
Status:
RECRUITING
Status Verified Date:
2024-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The planned study is a Randomized Controlled Monocentric Trial which will provide evidence on whether early angiography in PTA readiness immediate treatment within 48h has advantages over the standard of care ie an elective procedure elective PTA in terms of clinical endpoints such as wound healing and infection according to WiFI classification amputation rate major adverse limb events MALEamputation reintervention of the vessel death but also systemic complications such as major adverse cardiac and cerebrovascular events MACEmyocardial infarction stroke death restenosis severe cardiac and cerebrovascular complications Furthermore the impact of PTA on the local wound microbiome remains unclear Altered microbiome composition in ulcers can lead to severe local and systemic infections and complications including major amputations Nevertheless the specific significance of the wound microbiome composition in chronic ischemic ulcers in type 2 diabetes and the impact of PTA on the wound microbiome in type 2 diabetes is unclear The exact timing for treating pAVD by revascularization in DFS after initial diagnosis is unknown and has yet to be fully understood
Detailed Description:
The planned study is a monocentric randomized and controlled clinical trial Study participants will be randomized in a 11 ratio into a group with early PTA immediate PTA within 48h and a group with elective PTA standard of care Baseline and all follow-up examinations will be performed identically in both groups except for PTA The study is unblinded to the patients and physicians i e the investigators do not plan a control intervention for PTA However all subsequent laboratory tests especially the measurement of biomarkers of inflammation are designed to be blinded i e without passing information on PTA to the laboratory Baseline and follow-up examinations will focus on the severity and healing process of the foot ulcer If patients in the elective arm experience a significant deterioration in wound healing they are crossed to the immediate arm Thus for each of our patients the treatment of pAVD follows the guidelines which are controlled and documented by specialists in the clinical progress controls and visits during the study During the visits the investigators do not only pay attention to the diabetic foot ulcers but see each patient as a critically ill patient in the overall picture Thus the investigator first tried to improve renal retention parameters by sufficient hydration considering cardiac function In severe renal insufficiency guideline-based selective angiography on PTA standby using CO2 angiography is possible which does not affect the kidney
Baseline characterization The patients complete medical history and current and previous medications are obtained during the initial clinical evaluation In addition to the medical record lifestyle questions smoking alcohol and social status are elicited marital status educational attainmentsocial status
A physical examination is performed which includes determining whether venous or neuropathic triggers should be considered in addition to the ischemic etiology of the ulcers For evidence of chronic venous insufficiency CVI the investigators will perform duplex sonography of the peripheral leg veins If there is evidence of chronic venous insufficiency the severity will be evaluated using the Clinical C Etiological E Anatomical A and Pathophysiological P CEAP classification Routine laboratory chemistry testing will also be performed using blood samples In addition the diabetes mellitus duration will be recorded
Wound documentation Wound documentation is performed to document existing ulcerations The affected areas their depth and volume will be recorded This photo documentation should always be carried out at the same angle in the same position and distance and under the same lighting conditions as far as possible The wound is assessed according to the WIfI and Wagner Armstrong classification criteria recommended by current interdisciplinary guidelines
Perfusion measurement
The following examinations are performed
DuplexDoppler ultrasound of the leg arteries with Doppler frequency analysis and ankle-brachial and toe-ankle index measurement In the subsequent duplex ultrasound the anatomy of the peripheral arteries is defined Later in the course these examinations determine the patency of the revascularized vessel segment degree of stenosis by peak flow velocity determination and intimal hyperplasia Furthermore flow-dependent dilatation of the femoral artery is also examined using duplex sonography
Oxygen saturation of the foot will be analyzed using a spectroscopic camera its control measurement is done by measuring the hands
Segmental pulsoscillography
Measurement of arterial perfusion at rest and perfusion reserve using occlusion plethysmography
Hemodynamics blood pressure and heart rate
Pain at rest Recording of current clinical symptoms and pain questionnaire according to McGill
Peripheral neuropathy will be within the scope of the study the participating patients will also be examined for peripheral polyneuropathy based on the National Health Care Guideline NVL Neuropathy in Diabetes in Adulthood Peripheral nerve function tests include the clinical neuropathy score survey to diagnose diabetic sensorimotor polyneuropathy DSNP In detail the neuropathy symptom score NSS and the neuropathy deficit score NDS are recorded
Swab wound Specimen collection is performed according to the Levine method using a commercially available flocked swab FLOQSwab COPAN Diagnostics Inc Murrieta USA A total of 3 swabs will be taken from each patient in the project at the same time to obtain material for determining the microbiome and the corresponding resistogram specific transport media will be used depending on the downstream process Swabs are collected after thorough wound cleansing the first after initial wound care the second at four weeks the third at eight weeks the fourth at 12 weeks the fifth at 24 weeks and the last at 48 weeks
Measurements of phylogenetic composition based on the wound samples at baseline will determine the different bacterial species in the wound samples using whole genome sequencing in collaboration with the Institute of Medical Microbiology and Hospital Hygiene at Heinrich Heine University Düsseldorf The microbiomes composition is studied using nanopore technology which has several advantages Data are analyzed using custom bioinformatics scripts
Blood collection will be performed in the morning on an empty stomach Blood collections are performed id in a clinical routine before PTA and during the follow-up visits of the DFS and do not represent a study-related collection On this occasion additional blood samples can be taken without additional study-related punctures Blood will be collected in so-called stretch tubs for testing for cell-free cfDNA The time points include routine follow-up examinations on the first day of examination V0 on day 1 V1 one month V2 two months V3 three months V4 six months V5 12 months V6 after PTA Over the studys duration less than 500 ml of blood should be drawn per patient
Examination of cfDNA To assess the incorporation of microbial components from the revascularized tissues the investigators would like to determine the amount of microbial cfDNA A sufficient amount of the collected material will be assayed for a maximum period of three years
Statistical analysis Taxonomic profiling of whole-genome sequencing data of the wound microbiome is performed using bioinformatics scripts from the Department of Algorithmic Bioinformatics at HHU as previously described Whole-genome sequencing data of the wound microbiome generated with the Oxford Nanopore platform will be used for taxonomic profiling with Kraken2 and a comprehensive custom database of protozoan fungal viral and plant sequences Visualizations that allow comparison of metagenomic composition at different taxonomic levels are generated using custom scripts To evaluate the clustering of samples the investigators performed a principal coordinate analysis based on the Bray-Curtis distance Using the Conda version management system the entire workflow is provided as a reproducible Snakemake workflow Association of wound microbiome composition with metabolic phenotypes will be performed using omnibus blockwise and traitwise statistical models Variables will be compared using the Wilcoxon matched-pairs signed rank test the unpaired two-sided Student t-test and the two-sided Mann-Whitney U-test to detect differences over time and between groups Nominal variables are compared using the chi-square test and Fishers exact test as appropriate Relationships between variables eg associations between changes in microbiome composition and wound healing or complications will be assessed using partial Pearson correlation coefficients with and without adjustment for confounders and multiple testing using the Bonferroni method Standardized mean difference Cohens d was used for power analyses because preliminary estimates for the mean and standard error of the mean of wound microbiome change after PTA were not available in the literature All statistical analyses are performed using SPSS for Windows 230 SPSS Inc Chicago IL USA All graphs are generated using GraphPad Prism version 701 GraphPad Software Inc La Jolla CA USA
Baseline characterization The patients complete medical history and current and previous medications are obtained during the initial clinical evaluation In addition to the medical record lifestyle questions smoking alcohol and social status are elicited marital status educational attainmentsocial status
A physical examination is performed which includes determining whether venous or neuropathic triggers should be considered in addition to the ischemic etiology of the ulcers For evidence of chronic venous insufficiency CVI the investigators will perform duplex sonography of the peripheral leg veins If there is evidence of chronic venous insufficiency the severity will be evaluated using the Clinical C Etiological E Anatomical A and Pathophysiological P CEAP classification Routine laboratory chemistry testing will also be performed using blood samples In addition the diabetes mellitus duration will be recorded
Wound documentation Wound documentation is performed to document existing ulcerations The affected areas their depth and volume will be recorded This photo documentation should always be carried out at the same angle in the same position and distance and under the same lighting conditions as far as possible The wound is assessed according to the WIfI and Wagner Armstrong classification criteria recommended by current interdisciplinary guidelines
Perfusion measurement
The following examinations are performed
DuplexDoppler ultrasound of the leg arteries with Doppler frequency analysis and ankle-brachial and toe-ankle index measurement In the subsequent duplex ultrasound the anatomy of the peripheral arteries is defined Later in the course these examinations determine the patency of the revascularized vessel segment degree of stenosis by peak flow velocity determination and intimal hyperplasia Furthermore flow-dependent dilatation of the femoral artery is also examined using duplex sonography
Oxygen saturation of the foot will be analyzed using a spectroscopic camera its control measurement is done by measuring the hands
Segmental pulsoscillography
Measurement of arterial perfusion at rest and perfusion reserve using occlusion plethysmography
Hemodynamics blood pressure and heart rate
Pain at rest Recording of current clinical symptoms and pain questionnaire according to McGill
Peripheral neuropathy will be within the scope of the study the participating patients will also be examined for peripheral polyneuropathy based on the National Health Care Guideline NVL Neuropathy in Diabetes in Adulthood Peripheral nerve function tests include the clinical neuropathy score survey to diagnose diabetic sensorimotor polyneuropathy DSNP In detail the neuropathy symptom score NSS and the neuropathy deficit score NDS are recorded
Swab wound Specimen collection is performed according to the Levine method using a commercially available flocked swab FLOQSwab COPAN Diagnostics Inc Murrieta USA A total of 3 swabs will be taken from each patient in the project at the same time to obtain material for determining the microbiome and the corresponding resistogram specific transport media will be used depending on the downstream process Swabs are collected after thorough wound cleansing the first after initial wound care the second at four weeks the third at eight weeks the fourth at 12 weeks the fifth at 24 weeks and the last at 48 weeks
Measurements of phylogenetic composition based on the wound samples at baseline will determine the different bacterial species in the wound samples using whole genome sequencing in collaboration with the Institute of Medical Microbiology and Hospital Hygiene at Heinrich Heine University Düsseldorf The microbiomes composition is studied using nanopore technology which has several advantages Data are analyzed using custom bioinformatics scripts
Blood collection will be performed in the morning on an empty stomach Blood collections are performed id in a clinical routine before PTA and during the follow-up visits of the DFS and do not represent a study-related collection On this occasion additional blood samples can be taken without additional study-related punctures Blood will be collected in so-called stretch tubs for testing for cell-free cfDNA The time points include routine follow-up examinations on the first day of examination V0 on day 1 V1 one month V2 two months V3 three months V4 six months V5 12 months V6 after PTA Over the studys duration less than 500 ml of blood should be drawn per patient
Examination of cfDNA To assess the incorporation of microbial components from the revascularized tissues the investigators would like to determine the amount of microbial cfDNA A sufficient amount of the collected material will be assayed for a maximum period of three years
Statistical analysis Taxonomic profiling of whole-genome sequencing data of the wound microbiome is performed using bioinformatics scripts from the Department of Algorithmic Bioinformatics at HHU as previously described Whole-genome sequencing data of the wound microbiome generated with the Oxford Nanopore platform will be used for taxonomic profiling with Kraken2 and a comprehensive custom database of protozoan fungal viral and plant sequences Visualizations that allow comparison of metagenomic composition at different taxonomic levels are generated using custom scripts To evaluate the clustering of samples the investigators performed a principal coordinate analysis based on the Bray-Curtis distance Using the Conda version management system the entire workflow is provided as a reproducible Snakemake workflow Association of wound microbiome composition with metabolic phenotypes will be performed using omnibus blockwise and traitwise statistical models Variables will be compared using the Wilcoxon matched-pairs signed rank test the unpaired two-sided Student t-test and the two-sided Mann-Whitney U-test to detect differences over time and between groups Nominal variables are compared using the chi-square test and Fishers exact test as appropriate Relationships between variables eg associations between changes in microbiome composition and wound healing or complications will be assessed using partial Pearson correlation coefficients with and without adjustment for confounders and multiple testing using the Bonferroni method Standardized mean difference Cohens d was used for power analyses because preliminary estimates for the mean and standard error of the mean of wound microbiome change after PTA were not available in the literature All statistical analyses are performed using SPSS for Windows 230 SPSS Inc Chicago IL USA All graphs are generated using GraphPad Prism version 701 GraphPad Software Inc La Jolla CA USA
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None