Efficacy and Safety of Liraglutide in Type 2 Diabetes With Lower Extremity Arterial Disease

NCT04146155 | Unknown Phase 4 DMC

• 1 other identifier: zhengchao
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

Diabetic lower extremity arterial disease ( DLEAD ), is a common complication of type 2 diabetes. However, DLEAD remains less studied than other diabetic vascular complications; and only few randomised controlled trials (RCTs) have dealt with major lower-limb adverse events as prespecified endpoints. Studies have suggested that glucagon-like peptide-1 (GLP-1) analogues have a protective effect on the development of atherosclerosis, potentially mediated via the GLP-1 receptors expressed on endothelial cells, smooth muscle cells, and in monocytes/macrophages. The investigators aim to evaluate the improvement of lower extremity ischemia in patients with type 2 diabetes mellitus complicated with lower limb vascular lesions after liraglutide, compared with the standard-of-care treatment group.

Conditions

Type 2 Diabetes; Peripheral Vascular Disorder Due to Diabetes Mellitus

Keywords

Glucagon-like peptide-1; Claudication; Peripheral vascular disease

Outcome Measures

Primary Outcomes (1)

• Initial and absolute claudication distance

  The primary outcome measures used to assess efficacy were pain-free walking distance (distance walked to the onset of symptoms, or the initial claudication distance \[ICD\]) and the maximum distance walked (absolute claudication distance \[ACD\]) on standardized treadmill testing. Evaluation of walking performance was accomplished with standardized treadmill testing. A constant speed of 3.2 km/h (2mile/h) and a fixed incline of 12.5% were used.

  24 weeks

Secondary Outcomes (5)

• Assess the effects on ABI of a six month treatment with Liraglutide compared to control group (standard-of-care treatment).

  24 weeks

• Assess the effects on endothelial function of a six month treatment with Liraglutide compared to control group (standard-of-care treatment).

  24 weeks

• Muscle microvascular perfusion by CEU

  24 weeks

• Assess the effects on the endothelial circulating progenitor cells concentration of a six month treatment with Liraglutide compared to control group (standard-of-care treatment).

  24 weeks

• Changes from baseline in HbA1c

  24 weeks

Study Arms (2)

Liraglutide+standard-of-care treatment

EXPERIMENTAL

Intervention: Liraglutide is added to existing standard-of-care treatment containing one or more oral anti-hyperglycemic agents or insulin or a combination of these agents with the exception of other incretin and SGLT2i therapies.

Drug: Liraglutide+standard-of-care treatment

standard-of-care treatment

ACTIVE COMPARATOR

standard-of-care treatment with the exception of incretin and SGLT2i therapies. This approach expect to yield similar glycemic control in the two study groups.

Other: standard-of-care treatment

Interventions

Liraglutide+standard-of-care treatment DRUG

Liraglutide is available if pre-filled pens (6 mg/ml) as a solution for injection (Victoza®). One ml of solution contains 6 mg of Liraglutide (human glucagon-like peptide-1 analogue produced by recombinant DNA technology in Saccharomyces cerevisiae). One pre-filled pen contains 18 mg Liraglutide in 3 ml. Liraglutide is added to existing standard-of-care treatment containing one or more oral anti-hyperglycemic agents or insulin or a combination of these agents with the exception of other incretin and SGLT2i therapies in accordance with local clinical practice guidelines.

Also known as: Victoza

Liraglutide+standard-of-care treatment

standard-of-care treatment OTHER

Standard-of-care treatment including: metformin should be given as the first line therapy as long as it is tolerated and not contraindicated; other agents, including sulfonylureas or glucosidase inhibitor or insulin, should be added to metformin .Glycemic control will be managed by the investigators in accordance with local clinical practice guidelines by the adjustment of concomitant glucose-lowering agents or the addition of new antidiabetic medications with the exception of incretin and SGLT2i therapies. This approach expect to yield similar glycemic control in the two study groups.

standard-of-care treatment

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Informed consent
• type 2 diabetes (1999 WHO criteria)
• ≤HbA1c ≤14%
• Age \> 40 years
• lower extremity PAD with symptom
• Absence of distal arterial pulse.
• ABI less than 0.9 or the value decreased by more than 15% after treadmill test.
• Presence of stenosis or occlusion of lower extremity arteries as determined by Duplex ultrasound imaging or lower extremity CTA; or lower extremity DSA(Digital Substraction Angiography).

You may not qualify if:

• Type 1 diabetes
• Other Concomitant illness:
• \) poorly controlled hypertension: \>160 mmHg systolic blood pressure and/or\>100 mmHg diastolic blood pressure (with or without long-term oral antihypertensive drugs); 2) Chronic heart failure NYHA class (III-IV); 3) An acute coronary or cerebro-vascular event within the previous 6 months; 4) hematological malignancies such as acute or chronic myeloid leukemia, or any other hematological disorders that would interfere with the determination of circulating EPC levels; 5) Personal history of non-familial medullary thyroid carcinoma; 6) Immunological disorders such as lupus, psoriasis, scleroderma and rheumatoid arthritis which would interfere with the determination of circulating EPC levels; 7) Chronic haemodialysis or chronic peritoneal dialysis; 8) End stage liver disease, presence of acute or chronic liver disease or recent history of the following: ALT level ≥ 3 times the upper limit of normal, or AST level ≥ 3 times the upper limit of normal; 9) Severe gastrointestinal diseases, such as gastrointestinal ulcer, gastrointestinal bleeding, pyloric stenosis, gastric bypass surgery; 10) History of chronic pancreatitis or idiopathic acute pancreatitis; 11) Any acute condition or exacerbation of chronic condition that would in the Investigator's opinion interfere with the initial trial visit schedule and procedures; 12) Inability to walk on a tredamill without grade at a speed of at least 3.2 km/h for at least 2 minutes.
• Drugs: 1) Known or suspected hypersensitivity to trial products or related products ; 2) Use of GLP-1 receptor agonist (exenatide (BID or OW), liraglutide, or other) within 6 months prior to screening; 3).Alcohol or drugs abuse.
• \. Acute decompensation of glycaemic control requiring immediate intensification of treatment to prevent acute complications of diabetes (eg diabetes ketoacidosis) within 90 days prior to screening.
• Recent (within 6 months) surgery or trauma.
• Pregnancy and lactation.
• Psychiatric disorders
• Simultaneous participation in any other clinical trial of an investigational agent.

Sponsors & Collaborators

• Second Affiliated Hospital, School of Medicine, Zhejiang University: lead

Study Sites (1)

The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University

Wenzhou, Zhejiang, 325000, China

RECRUITING

Related Publications (1)

• Kanie T, Mizuno A, Takaoka Y, Suzuki T, Yoneoka D, Nishikawa Y, Tam WWS, Morze J, Rynkiewicz A, Xin Y, Wu O, Providencia R, Kwong JS. Dipeptidyl peptidase-4 inhibitors, glucagon-like peptide 1 receptor agonists and sodium-glucose co-transporter-2 inhibitors for people with cardiovascular disease: a network meta-analysis. Cochrane Database Syst Rev. 2021 Oct 25;10(10):CD013650. doi: 10.1002/14651858.CD013650.pub2.

  PMID: 34693515 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Intermittent Claudication; Peripheral Vascular Diseases

Interventions

Liraglutide

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Peripheral Arterial Disease; Vascular Diseases; Cardiovascular Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide 1; Glucagon-Like Peptides; Proglucagon; Gastrointestinal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Chao Zheng, MD,PhD

  the Second Affiliated Hospital Zhejiang University Schoolof Medicine

  PRINCIPAL INVESTIGATOR

• Youjin Pan, MD.

  Second Affiliated Hospital of Wenzhou Medical University

  PRINCIPAL INVESTIGATOR

• Xia Li, MD,PhD

  Central South University

  PRINCIPAL INVESTIGATOR

• Li Li, MD.

  Ningbo Hospital of Zhejiang University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Chao Zheng, MD, PhD

CONTACT

8615057585907; wallbb_1022@163.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 16, 2019
• First Posted: October 31, 2019
• Study Start: May 1, 2020
• Primary Completion: December 31, 2021
• Study Completion: December 31, 2021
• Last Updated: July 7, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)