DIAbetes Maximal ACCeleration

Not Applicable

Not yet recruiting

• Conditions: Diagnosis; Peripheral Arterial Disease; Diabetic Foot
• Interventions: Device: Maximal Systolic Acceleration

• Registration Number: NCT05646147
• Lead Sponsor: Leiden University Medical Center

Brief Summary

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.

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 Timeline

• Study First Submitted: 2022-11-20
• Study First Submitted QC: 2022-12-02
• Study First Posted: 2022-12-12
• Status Verified: 2023-03
• Last Update Submitted: 2023-03-08
• Last Update Posted: 2023-03-10
• Study Start: 2023-07
• Primary Completion: 2025-01
• Study Completion: 2025-07

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 238

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Diagnostic Cohort Study	Maximal Systolic Acceleration	All patients will underwent full diagnostic testing.

Primary Outcome Measures

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

Secondary Outcome Measures

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