DIAbetes Maximal ACCeleration (DIAMACC)

Diagnostic Accuracy of the Maximal Systolic Acceleration for Detection of Peripheral Arterial

Prevalence of diabetes mellitus (DM) is increasing rapidly, with patient numbers projected to rise to 643 million by 2030. As a consequence of diabetes-related atherosclerosis, peripheral arterial disease (PAD) and in particular medial arterial calcification (MAC) can occur. The accurate identification of PAD by bedside tests is extremely important in patients with diabetes and foot ulceration, in order to reduce delayed wound healing, prevent lower limb amputation and eventually reduce mortality. However, as shown in previous systematic reviews, the performance of current bedside tests is not reliable in excluding PAD in diabetic patients.1,2 Moreover, the methodological quality of the conducted studies is generally poor. Therefore, more reliable and prospective data is required. Also alternative bedside tests need to be investigated. As an example, the ACCmax (a new doppler derived parameter) could be particularly promising in this patient group.

Study Overview

• Status: Not yet recruiting
• Conditions: Diabetic Foot; Peripheral Arterial Disease; Diagnosis
• Intervention / Treatment: Device: Maximal Systolic Acceleration

Detailed Description

According to the latest 2021 data from the International Diabetes Federation, an estimated 537 million adults are living with DM globally.3 Prevalence is increasing rapidly, with numbers projected to rise to 643 million by 2030 and 783 million by 2045. Annually, DM causes 6.7 million deaths, as a consequence of both macrovascular- (atherosclerosis) and microvascular disease (retinopathy, nephropathy, and neuropathy). In 2021, diabetes caused at least 966 billion dollars in health expenditure, comprising approximately 9% of total spending on adults. Type 2 diabetes comprises about 85-90% of these cases, in which disease onset is often insidious, and diagnosis is consequently delayed.4

Peripheral arterial disease (PAD) of the lower extremity is a clinical manifestation of systemic atherosclerosis and considered a well-known (long-term) complication of DM. Besides atherosclerosis, calcification of the tunica media of the arterial wall can occur. This process is called medial arterial calcification (MAC) and is accelerated in the presence of DM. Research suggests that MAC is present in approximately one third of patients with DM.5 MAC has been shown to be an independent predictor of cardiovascular mortality, while another study found that patients with DM and PAD have an impaired quality of life and an increased risk of adverse cardiac and limb events.6,7

Timely recognition of limb ischemia is important in patients with DM/MAC in order to reduce delayed wound healing, prevent lower limb amputation and eventually reduce mortality.8 Current non-invasive bedside tests - such as the ankle-brachial index (ABI) and toe pressure (TP) - are considered accurate for the diagnosis of PAD. However, as shown in previous systematic reviews, the performance of current bedside tests is not reliable in excluding PAD in diabetic patients.1,2 The methodological quality of the studies in these reviews were poor. In general, most of the data was collected retrospectively and not all patients received reference testing. In order to assess the reliability of bedside tests in this patient group, more well-sound methodological research is required. Also alternative bedside tests need to be investigated.

The doppler derived maximal systolic acceleration (ACCmax) is a new non-invasive parameter, which could be promising in detecting PAD. Although ACCmax has already been used for renal artery stenosis9, thorough evaluation has not been performed in PAD. Two previous studies showed accurate diagnostic property in diabetic patients, but the sample sizes were small.10,11

The aim of this study is to assess the clinical value of bedside tests compared to DUS to detect PAD in patients with diabetes-related foot ulceration, with special emphasis on the ACCmax.

• Study Type: Interventional
• Enrollment (Anticipated): 238
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Siem Willems, MD; Phone Number: +31642642819; Email: s.a.willems@lumc.nl

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 18 years or older.
• DM in medical history.
• Presenting with a new-onset wound or ulceration on the foot or ankle with initiation of a new diagnostic care path.

Exclusion Criteria:

- Lacking capacity to consent for inclusion.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Diagnostic Cohort Study; All patients will underwent full diagnostic testing.	Device: Maximal Systolic Acceleration; Reliability of the maximal systolic acceleration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reliability of standard bedside tests and the maximal systolic acceleration (ACCmax)	Sensitivity and specificity including their derivates: PLR and NLR	Through study completion, approximately 1.5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of ACCmax reliability with current bedside tests	Comparison of ACCmax reliability with current bedside tests	Through study completion, approximately 1.5 years
Comparison of patient demographics (such as age/sex) and comorbidities (duration of diabetes, chronic kidney disease) with diagnostic accuracy of different bedside tests	Comparison of patient demographics (such as age/sex) and comorbidities (duration of diabetes, chronic kidney disease) with diagnostic accuracy of different bedside tests	Through study completion, approximately 1.5 years
Wound healing and ACCmax	To assess if the maximal systolic acceleration can predict wound healing	Up to 5 years after study completion

Collaborators and Investigators

• Sponsor: Leiden University Medical Center

Study record dates

Study Major Dates

• Study Start (Anticipated): July 1, 2023
• Primary Completion (Anticipated): January 1, 2025
• Study Completion (Anticipated): July 1, 2025

Study Registration Dates

• First Submitted: November 20, 2022
• First Submitted That Met QC Criteria: December 2, 2022
• First Posted (Actual): December 12, 2022

Study Record Updates

• Last Update Posted (Estimate): March 10, 2023
• Last Update Submitted That Met QC Criteria: March 8, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Diagnosis; Peripheral Arterial Disease; Diabetic Foot
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Endocrine System Diseases; Diabetic Angiopathies; Leg Ulcer; Skin Ulcer; Diabetes Complications; Diabetes Mellitus; Diabetic Neuropathies; Atherosclerosis; Foot Ulcer; Diabetic Foot; Peripheral Arterial Disease; Peripheral Vascular Diseases
• Other Study ID Numbers: LUMC-DIAMACC

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