Intestinal Ischemia Biomarker in Patients With Chronic Mesenteric Ischemia

Intestinal Ischemia Biomarker and Quality of Life of the Patients With Chronic Mesenteric Ischemia and Median Arcuate Ligament Syndrome

Plasma Alpha glutathione S transferase (Alpha GST) has been previously demonstrated to be raised in patients with chronic mesenteric ischemia (CMI) caused by atherosclerosis and in patients with median arcuate ligament syndrome (MALS). Raised plasma level of Alpha GST has been demonstrated to decrease or normalize after surgical treatment of patients with CMI and MALS as compared with healthy individuals.

This study compares the plasma Alpha GST in patients with CMI and MALS with those with 1-Morbus Crohn, 2-Gallstone disease, and age-matched healthy individuals.

Besides, changes in the health-related quality of life (QoL) will be investigated in the study individuals.

Study Overview

• Status: Recruiting
• Conditions: Crohn Disease; Cholelithiasis; Chronic Mesenteric Ischemia; Median Arcuate Ligament Syndrome
• Intervention / Treatment: Procedure: Laparoscopic surgery

Detailed Description

Patients with CMI and MALS usually complain of postprandial abdominal pain, changes in food intake pattern, and weight loss. These symptoms are often shared with many other more common diseases. Therefore, the diagnosis of CMI, and especially MALS, is often an exclusion diagnosis. To this date, no biomarker of intestinal ischemia with sufficient sensitivity and specificity has been identified for routine clinical use.

In a previous study, raised levels of plasma Alpha glutathione S transferase (Alpha GST) (7.8 ng/mL) in patients with CMI caused by atherosclerosis and in the patients with MALS (8.4 ng/mL). The raised plasma level of Alpha GST has been demonstrated to decrease or normalize after surgical improvement of the intestinal circulation in patients with CMI and MALS as compared with healthy individuals (3.3 ng/mL). However, the study was not appropriately powered and did not include a control group with similar clinical symptoms as in the patients with CMI and MALS.

This study will compare the plasma Alpha GST levels in patients with CMI (n=30) and MALS (n=30) with 1-Morbus Crohn (n=30), 2-Gallstone disease (n=30), and age-matched healthy individuals (n=60).

The CMI and MALS patients diagnosed with CTA and duplex ultrasound and scheduled to have either endovascular (PTA or stent) or open surgery (mesenteric bypass ) treatment will be included in this study.

Duplex ultrasound will be used to exclude CMI and MALS in the individuals in the control groups. After inclusion in the study, venous blood samples will be taken to exclude renal failure and liver disease. The blood samples will be repeated within 3 months. The blood samples will be centrifuged and stored at -70 degrees until analyzed in batches with the ELISA technique. Participants in the control groups will be examined with duplex ultrasound at the time of inclusion in the study and agian at three months.

In the patient groups, i.e., CMI and MALS, the venous blood samples will be obtained before and 3 months after the treatment. The blood samples will be centrifuged and stored at -70 degrees until analyzed in batches with the ELISA technique.

The plasma levels of Alpha GST will be compared beside receiver operating characteristic curves (ROC), and the area under the curve(AUC) will be calculated.

In addition to Alpha GST, the plasma of the study individuals will also be tested for other potential markers of intestinal ischemia, i.e., intestinal fatty acid binding protein (i-FABP), citrulline, and ischemia-modified albumin (IMA).

The study will also follow the patients participating in the study for clinical changes in symptoms. In addition, patient demographics, comorbidities, treatment demographics, and complications of the treatment will be registered. A questionnaire has been constructed for the patient groups in the study to register the clinical signs and symptoms. The patients will fill out the questionnaire before and after the treatment. The study patients will be followed up after treatment at the outpatient clinic at 1 and 3 months and at 1, 2, 5, and 10 years. Duplex ultrasound will be performed at all follow-up time points.

Furthermore, changes in the health-related quality of life (QoL) will be investigated in the study individuals. The EuroQol 5D (EQ5D) questionnaire will be used to assess the QoL of the study patients. The patients will fill out the EQ5D at inclusion in the study and 1, 2, 5, and 10 years after treatment of CMI and MALS in the patient groups. EQ-5D can be converted to a single summary index by applying a formula that attaches weight to each of the levels in each dimension. The EQ-5D index is varying between 0 to 1 where 1 presents best health condition and 0 presenting the worst health state .

Information from the quality of life and the costs of treatment during the hospital stay will be used to estimate the quality-adjusted life years (QALY) and the cost-utility of treating patients with CMI and MALS.

• Study Type: Observational
• Enrollment (Estimated): 180

Contacts and Locations

• Study Contact: Name: Syed Sajid Hussain Kazmi, MD, PhD; Phone Number: 4792468309; Email: sshkazmi@gmail.com

Study Locations

• Norway
  • Oslo, Norway
    • Recruiting
    • Department of vascular surgery, Oslo University Hospital
    • Contact: Syed Sajid Hussain Kazmi, MD, PhD; Phone Number: 004792468309; Email: sshkazmi@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

CMI and MALS patients with the vascular surgery department, Oslo University Hospital, with a consensus diagnosis of MALS and a diagnosis of CMI and schedules operative or endovascular treatment.

Control groups are the individuals under treatment with the Oslo University Hospital or regular blood donors at the hospital.

Description

Inclusion Criteria: Above 18 years and has given informed written consent for treatment and study participation

For the patient groups :

Group 1: Has CTA or ultrasound diagnosed MALS and is scheduled operative treatment.

Group 2: Has CTA or ultrasound diagnosed CMI and is scheduled operative or endovascular treatment.

For the control group:

Group 3- Has ultrasound based diagnosis of cholelithiasis and is scheduled for cholecystectomy.

Group 4- Has established Mb Crohn diagnosis and under gastric lab follow-up. Group 5- Young healthy blood donors of mean age 45 years and has excluded MALS or CMi with ultrasound.

Group 6- Healthy blood donors of mean age 70 years and has excluded MALS or CMi with ultrasound.

Exclusion Criteria: Age less than 18 years Has nor given written consent.

-

Study Plan

How is the study designed?

Number of groups / cohorts

6

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Median arcuate ligament syndrome (MALS); Patients with MALS Scheduled for laparoskopic decompression.	Procedure: Laparoscopic surgery; The patients in the MALS group will be treated through transperitoneal ventral approach for the laparoscopic release of the celiac artery. Median arcuate ligament and any muscle or nerve tissue crossing the cranial surface of the celiac artery will be divided to release the celiac artery from compression. In the patients with CMI open antegrade or retrograde bypass to celiac artery or superior mesenteric artery or both will be performed. For operative treatment will be performed in general anaethesia whereas the endovacular treatment with PTA with stent for CMI will be performed in local anaethesia.; Other Names: Percutaneous transluminal angioplasty (PTA) with stent; Open mesenteric bypass
Chronic mesenteric ischemia (CMI); Patients with CMI caused by atherosclerotic stenosis or occlusion of celiac artery, superior mesenteric artery ( one or both arteries ), and scheduled treatment with either PTA/stent or mesenteric bypass.	Procedure: Laparoscopic surgery; The patients in the MALS group will be treated through transperitoneal ventral approach for the laparoscopic release of the celiac artery. Median arcuate ligament and any muscle or nerve tissue crossing the cranial surface of the celiac artery will be divided to release the celiac artery from compression. In the patients with CMI open antegrade or retrograde bypass to celiac artery or superior mesenteric artery or both will be performed. For operative treatment will be performed in general anaethesia whereas the endovacular treatment with PTA with stent for CMI will be performed in local anaethesia.; Other Names: Percutaneous transluminal angioplasty (PTA) with stent; Open mesenteric bypass
Morbus Crohn intestine; Patients with diagnosed Mb Crohn of intestine who does not have CMI or MALS excluded with duplex ultrasound.
Cholilithiasis; Patients with diagnosed Cholilithiasis who is scheduled for operative chelecystectomy and does not have CMI or MALS, excluded with the help of duplex ultrasound.
Blood donor (Young); Healthy blood donor with a median age of 45 years, who does not have symptoms of mesenteric ischemia or MALS and has excluded these two conditions with the help of duplex ultrasound.
Blood donor (Old); Healthy blood donor with a median age of 70 years, who does not have symptoms of mesenteric ischemia or MALS and has excluded these two conditions with the help of duplex ultrasound.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma alpha Glutathione S transferase	This study compares the plasma Alpha GST in patients with CMI (n=30) and MALS (n=30) with those with 1-Morbus Crohn (n=30), 2-Gallstone disease (n=30), and age-matched healthy individuals (n=60). After inclusion in the study, blood tests will be performed to exclude renal failure and liver disease. Venous blood samples will be obtained before and 3 months after treatment in the patients with CMI and MALS. Blood samples will also be obtained from the individuals in the control groups twice ( at inclusion and 3 months apart ). The blood samples will be centrifuged and stored at -70 degrees until analyzed in batches with the ELISA technique. The plasma levels of Alpha GST in ng/mL before and after the intervention will be compared seperately for the differnt study groups.	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cost utility analysis of the treatment of CMI and MALS	Quality adjusted life years (QALY ) estimation of the surgical and endovascular treatment of the patients with CMI and MALS. The costs of the treatment during the hospital stay will be calculated, compared with the costs of treatment given by the Norwegian Directorate of Health, QALY will be calculated based on the EQ5D results and the estimated treatment costs.	5 years
Health related quality of life (QoL)	Changes in the health-related quality of life (QoL) will be investigated. EuroQol 5D (EQ5D) questionnaire, which is a generic tool, will be used to assess the QoL of the study patients. EQ5D is a generic tool for the assessment of health related quality of life and is translated to Norwegian language and validated tool for the assessmeent of changes in the health related quality of life. The patients will fill out the EQ5D at inclusion in the study and 1, 2, 5, and 10 years after treatment of CMI and MALS in the patient groups. EQ5D has 5 questions with 5 levels of answers to each question. Level 1 will denote the best possible health status and level 5 denotes the worst health status for each of the 5 questions. It allows to a assess both physical and mental quality of health of the patients.	5 years
Clinical outcomes of the treatment of CMI and MALS	Effect of treatment on the symptoms of CMI and MALS postoperatively at 30 and 90 days, and at 1, 2, 5 and 10 years. A study specific questionnaire has been deveolped to register the signs and symptoms of CMI and MALS. The patients in the study will fill-out the questionnaire before and after the treatment and will repeat it at every follow-up time-point. The patients in the study will be follow-up by the clinicians who are not directly involved with the study and therefore the clinical information obtained will be standarized and made independent of the clinician's background. The questionnaire will allow to assess if the clinical symptoms have improved or worsen during the follow-up.	10 years
Intestinal ishemia biomarkers for CMI and MALS	Secondary outcome mesure: Plasma levels of intestinal fatty acid binding protein (iFABP) in ng/mL. In the previous studies, this biomarker has been demonstrated to be raised in the plasma of patients with CMI. Venous blood obtained fra the study individuals before and 3 months after the treatment of CMI and MALS will be analyzed with ELISA technique to discover any changes in these plasma biomarkers of ischemia. The groups will be compared for the changes in the individual plasma levels of these biomarkers and tested for any association to intestinal ischemia.	3 months
Plasma citruline	Plasma citroline is shown to be raised in the plasma of CMI patients in the previous studies. Venous blood samples will be taken before and 3 months after treatment of CMI and MALS patients and stored at -70 degrees until analyzed to find diffrences before and after the treatment and compare the diffrent study groups.	3 months
Immune modified albumin (IMA)	Immune modified albumin (IMA) in ng/mL is shown to be raised in the blood samples of patients with CMI. Venous blood samples will be taken before and 3 months after treatment of study patients with MALS, CMI and control groups. The blood samples will be analyzed to compare the plasma levels before and after the treatment of CMI and MALS and also compared with the control groups.	3 months

Collaborators and Investigators

• Sponsor: Oslo University Hospital
• Investigators: Principal Investigator: Syed Sajid Hussain Kazmi, MD, PhD, Department of vascular surgery, Oslo University Hospital

Publications and helpful links

General Publications

• Kazmi SSH, Safi N, Berge ST, Kazmi M, Sundhagen JO, Julien K, Thorsby PM, Anonsen KV, Medhus AW, Hisdal J. Plasma alpha-Glutathione S-Transferase in Patients with Chronic Mesenteric Ischemia and Median Arcuate Ligament Syndrome. Vasc Health Risk Manag. 2022 Jul 21;18:567-574. doi: 10.2147/VHRM.S365625. eCollection 2022.

Study record dates

Study Major Dates

• Study Start (Actual): June 10, 2024
• Primary Completion (Estimated): May 31, 2037
• Study Completion (Estimated): May 31, 2037

Study Registration Dates

• First Submitted: June 12, 2024
• First Submitted That Met QC Criteria: June 16, 2024
• First Posted (Actual): June 21, 2024

Study Record Updates

• Last Update Posted (Actual): July 30, 2025
• Last Update Submitted That Met QC Criteria: July 29, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: MALS; Chronic mesenteric ischemia; Intestinal ishchemia biomarker; alpha GST
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Disease Attributes; Intestinal Diseases; Digestive System Diseases; Gastrointestinal Diseases; Biliary Tract Diseases; Gastroenteritis; Inflammatory Bowel Diseases; Congenital Abnormalities; Cardiovascular Abnormalities; Peritoneal Diseases; Arterial Occlusive Diseases; Vascular Malformations; Digestive System Abnormalities; Median Arcuate Ligament Syndrome; Ischemia; Crohn Disease; Cholelithiasis; Chronic Disease; Mesenteric Ischemia
• Other Study ID Numbers: 607155

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No