Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Trials
Published in: Trials 1/2017

Open Access 01-12-2017 | Study protocol

Inositol in the MAnaGemENt of abdominal aortic aneurysm (IMAGEN): study protocol for a randomised controlled trial

Authors: Sophie E. Rowbotham, Jenna L. Pinchbeck, Georgina Anderson, Bernie Bourke, Michael Bourke, T. Christian Gasser, Rene Jaeggi, Jason S. Jenkins, Corey S. Moran, Susan K. Morton, Christopher M. Reid, Ramesh Velu, Lisan Yip, Joseph V. Moxon, Jonathan Golledge

Published in: Trials | Issue 1/2017

Login to get access

Abstract

Background

An abdominal aortic aneurysm (AAA) is a focal dilation of the abdominal aorta and is associated with a risk of fatal rupture. Experimental studies suggest that myo-inositol may exert beneficial effects on AAAs through favourable changes to biological pathways implicated in AAA pathology. The aim of the Inositol in the MAnaGemENt of abdominal aortic aneurysm (IMAGEN) trial is to assess if myo-inositol will reduce AAA growth.

Methods/design

IMAGEN is a multi-centre, prospective, parallel-group, randomised, double-blind, placebo-controlled trial. A total of 164 participants with an AAA measuring ≥ 30 mm will be randomised to either 2 g of myo-inositol or identical placebo twice daily for 12 months. The primary outcome measure will be AAA growth estimated by increase in total infrarenal aortic volume measured on computed tomographic scans. Secondary outcome measures will include AAA diameter assessed by computed tomography and ultrasound, AAA peak wall stress and peak wall rupture index, serum lipids, circulating AAA biomarkers, circulating RNAs and health-related quality of life. All analysis will be based on the intention-to-treat principle at the time of randomisation. All patients who meet the eligibility criteria, provide written informed consent and are enrolled in the study will be included in the primary analysis, regardless of adherence to dietary allocation.

Discussion

Currently, there is no known medical therapy to limit AAA progression. The IMAGEN trial will be the first randomised trial, to our knowledge, to assess the value of myo-inositol in limiting AAA growth.

Trial registration

Australian New Zealand Clinical Trials Registry, ACTRN12615001209​583. Registered on 6 November 2015.
Appendix
Available only for authorised users
Literature
1.
2.
Khosla S, et al. Meta-analysis of peak wall stress in ruptured, symptomatic and intact abdominal aortic aneurysms. Br J Surg. 2014;101(11):1350–7.CrossRefPubMed
3.
Norman PE, Muller J, Golledge J. The cardiovascular and prognostic significance of the infrarenal aortic diameter. J Vasc Surg. 2011;54(6):1817–20.CrossRefPubMed
4.
Cao P, et al. Comparison of surveillance versus aortic endografting for small aneurysm repair (CAESAR): results from a randomised trial. Eur J Vasc Endovasc Surg. 2011;41(1):13–25.CrossRefPubMed
5.
Lederle FA, et al. Immediate repair compared with surveillance of small abdominal aortic aneurysms. N Engl J Med. 2002;346(19):1437–44.CrossRefPubMed
6.
Ouriel K, et al. Endovascular repair compared with surveillance for patients with small abdominal aortic aneurysms. J Vasc Surg. 2010;51(5):1081–7.CrossRefPubMed
7.
United Kingdom Small Aneurysm Trial Participants. Long-term outcomes of immediate repair compared with surveillance of small abdominal aortic aneurysms. N Engl J Med. 2002;346(19):1445–52.CrossRef
8.
Golledge J, et al. Abdominal aortic aneurysm: pathogenesis and implications for management. Arterioscler Thromb Vasc Biol. 2006;26(12):2605–13.CrossRefPubMed
9.
Golledge J, Norman PE. Current status of medical management for abdominal aortic aneurysm. Atherosclerosis. 2011;217(1):57–63.CrossRefPubMed
10.
EVAR trial participants. Endovascular aneurysm repair versus open repair in patients with abdominal aortic aneurysm (EVAR trial 1): randomised controlled trial. Lancet. 2005;365(9478):2179–86.CrossRef
11.
12.
Hayter CL, et al. Follow-up costs increase the cost disparity between endovascular and open abdominal aortic aneurysm repair. J Vasc Surg. 2005;42(5):912–8.CrossRefPubMed
13.
UK Small Aneurysm Trial Participants. Health service costs and quality of life for early elective surgery or ultrasonographic surveillance for small abdominal aortic aneurysms. Lancet. 1998;352(9141):1656–60.CrossRef
14.
Robertson L, Atallah E, Stansby G. Pharmacological treatment of vascular risk factors for reducing mortality and cardiovascular events in patients with abdominal aortic aneurysm. Cochrane Database Syst Rev. 2014;1:CD010447.
15.
Golledge J, et al. Challenges and opportunities in limiting abdominal aortic aneurysm growth. J Vasc Surg. 2017;65(1):225–33.CrossRefPubMed
16.
D’Anna R, et al. Effects of a new flavonoid and myo-inositol supplement on some biomarkers of cardiovascular risk in postmenopausal women: a randomized trial. Int J Endocrinol. 2014;2014:653561.PubMedPubMedCentral
17.
Giordano D, et al. Effects of myo-inositol supplementation in postmenopausal women with metabolic syndrome: a perspective, randomized, placebo-controlled study. Menopause. 2011;18(1):102–4.CrossRefPubMed
18.
Maeba R, et al. Myo-inositol treatment increases serum plasmalogens and decreases small dense LDL, particularly in hyperlipidemic subjects with metabolic syndrome. J Nutr Sci Vitaminol (Tokyo). 2008;54(3):196–202.CrossRef
19.
Santamaria A, et al. One-year effects of myo-inositol supplementation in postmenopausal women with metabolic syndrome. Climacteric. 2012;15(5):490–5.CrossRefPubMed
20.
Clements Jr RS, Darnell B. Myo-inositol content of common foods: development of a high-myo-inositol diet. Am J Clin Nutr. 1980;33(9):1954–67.PubMed
21.
Estruch R, et al. Primary prevention of cardiovascular disease with a Mediterranean diet. N Engl J Med. 2013;368(14):1279–90.CrossRefPubMed
22.
Stackelberg O, et al. Fruit and vegetable consumption with risk of abdominal aortic aneurysm. Circulation. 2013;128(8):795–802.CrossRefPubMed
23.
Billcliff PG, Lowe M. Inositol lipid phosphatases in membrane trafficking and human disease. Biochem J. 2014;461(2):159–75.CrossRefPubMed
24.
Croze ML, Soulage CO. Potential role and therapeutic interests of myo-inositol in metabolic diseases. Biochimie. 2013;95(10):1811–27.CrossRefPubMed
25.
Ivanova H, et al. Inositol 1,4,5-trisphosphate receptor-isoform diversity in cell death and survival. Biochim Biophys Acta. 2014;1843(10):2164–83.CrossRefPubMed
26.
Condé C, et al. The inositol phosphatase SHIP-1 inhibits NOD2-induced NF-κB activation by disturbing the interaction of XIAP with RIP2. PLoS One. 2012;7(7):e41005.CrossRefPubMedPubMedCentral
27.
Gold MJ, et al. Lineage-specific regulation of allergic airway inflammation by the lipid phosphatase Src homology 2 domain-containing inositol 5-phosphatase (SHIP-1). J Allergy Clin Immunol. 2015;136(3):725–36. e2.CrossRefPubMed
28.
Kapral M, et al. Inhibitory effect of inositol hexaphosphate on metalloproteinases transcription in colon cancer cells stimulated with phorbol-12-myristate 13-acetate. Acta Pol Pharm. 2012;69(6):1307–12.PubMed
29.
Kapral M, et al. The effect of inositol hexaphosphate on the expression of selected metalloproteinases and their tissue inhibitors in IL-1β-stimulated colon cancer cells. Int J Colorectal Dis. 2012;27(11):1419–28.CrossRefPubMedPubMedCentral
30.
31.
Semini G, et al. Inositol-C2-PAF down-regulates components of the antigen presentation machinery in a 2D-model of epidermal inflammation. Biochem Pharmacol. 2014;87(3):477–88.CrossRefPubMed
32.
33.
Miyake T, et al. Regression of abdominal aortic aneurysms by simultaneous inhibition of nuclear factor κB and Ets in a rabbit model. Circ Res. 2007;101(11):1175–84.CrossRefPubMed
34.
Moran CS, et al. Osteoprotegerin deficiency limits angiotensin II-induced aortic dilatation and rupture in the apolipoprotein E-knockout mouse. Arterioscler Thromb Vasc Biol. 2014;34(12):2609–16.CrossRefPubMedPubMedCentral
35.
Moran CS, et al. Association of osteoprotegerin with human abdominal aortic aneurysm progression. Circulation. 2005;111(23):3119–25.CrossRefPubMed
36.
Saito T, et al. Importance of endothelial NF-κB signalling in vascular remodelling and aortic aneurysm formation. Cardiovasc Res. 2013;97(1):106–14.CrossRefPubMed
37.
Yang Z. Endothelial NF-κB: the remote controller of the backyard fire in the vascular wall? Cardiovasc Res. 2013;97(1):8–9.CrossRefPubMed
38.
Nakashima H, et al. Inhibition of experimental abdominal aortic aneurysm in the rat by use of decoy oligodeoxynucleotides suppressing activity of nuclear factor κB and Ets transcription factors. Circulation. 2004;109(1):132–8.CrossRefPubMed
39.
40.
Moran CS, et al. Everolimus limits aortic aneurysm in the apolipoprotein E-deficient mouse by downregulating C-C chemokine receptor 2 positive monocytes. Arterioscler Thromb Vasc Biol. 2013;33(4):814–21.CrossRefPubMed
41.
Rouer M, et al. Rapamycin limits the growth of established experimental abdominal aortic aneurysms. Eur J Vasc Endovasc Surg. 2014;47(5):493–500.CrossRefPubMed
42.
43.
Bruemmer D, et al. Angiotensin II-accelerated atherosclerosis and aneurysm formation is attenuated in osteopontin-deficient mice. J Clin Invest. 2003;112(9):1318–31.CrossRefPubMedPubMedCentral
44.
Golledge J, et al. Association between osteopontin and human abdominal aortic aneurysm. Arterioscler Thromb Vasc Biol. 2007;27(3):655–60.CrossRefPubMed
45.
Matarrelli B, et al. Effect of dietary myo-inositol supplementation in pregnancy on the incidence of maternal gestational diabetes mellitus and fetal outcomes: a randomized controlled trial. J Matern Fetal Neonatal Med. 2013;26(10):967–72.CrossRefPubMed
46.
Mukai T, et al. A meta-analysis of inositol for depression and anxiety disorders. Hum Psychopharmacol. 2014;29(1):55–63.CrossRefPubMed
47.
Golledge J, et al. Obesity, adipokines, and abdominal aortic aneurysm: Health in Men study. Circulation. 2007;116(20):2275–9.CrossRefPubMed
48.
49.
Golledge J, et al. Association between serum lipoproteins and abdominal aortic aneurysm. Am J Cardiol. 2010;105(10):1480–4.CrossRefPubMed
50.
Moxon JV, et al. Comparison of the serum lipidome in patients with abdominal aortic aneurysm and peripheral artery disease. Circ Cardiovasc Genet. 2014;7(1):71–9.CrossRefPubMed
51.
Golledge J, Norman PE. Pathophysiology of abdominal aortic aneurysm relevant to improvements in patients’ management. Curr Opin Cardiol. 2009;24(6):532–8.CrossRefPubMed
52.
De Grazia S, et al. Myo-inositol soft gel capsules may prevent the risk of coffee-induced neural tube defects. Expert Opin Drug Deliv. 2012;9(9):1033–9.CrossRefPubMed
53.
Parr A, et al. Comparison of volume and diameter measurement in assessing small abdominal aortic aneurysm expansion examined using computed tomographic angiography. Eur J Radiol. 2011;79(1):42–7.CrossRefPubMed
54.
The Australia and New Zealand Society of Vascular Surgery. The Australian Vascular Audit. February 2014.
55.
Vammen S, et al. Randomized double-blind controlled trial of roxithromycin for prevention of abdominal aortic aneurysm expansion. Br J Surg. 2001;88(8):1066–72.CrossRefPubMed
56.
Lederle FA, et al. Rupture rate of large abdominal aortic aneurysms in patients refusing or unfit for elective repair. JAMA. 2002;287(22):2968–72.CrossRefPubMed
57.
Jayalath RW, Jackson P, Golledge J. Quantification of abdominal aortic calcification on CT. Arterioscler Thromb Vasc Biol. 2006;26(2):429–30.CrossRefPubMed
58.
Parr A, et al. Thrombus volume is associated with cardiovascular events and aneurysm growth in patients who have abdominal aortic aneurysms. J Vasc Surg. 2011;53(1):28–35.CrossRefPubMedPubMedCentral
59.
Rai D, et al. Abdominal aortic aneurysm calcification and thrombus volume are not associated with outcome following endovascular abdominal aortic aneurysm repair. Eur Radiol. 2014;24(8):1768–76.CrossRefPubMed
60.
61.
Martufi G, et al. Multidimensional growth measurements of abdominal aortic aneurysms. J Vasc Surg. 2013;58(3):748–55.CrossRefPubMed
62.
Gasser TC, et al. A novel strategy to translate the biomechanical rupture risk of abdominal aortic aneurysms to their equivalent diameter risk: method and retrospective validation. Eur J Vasc Endovasc Surg. 2014;47(3):288–95.CrossRefPubMed
63.
Golledge J, et al. Evaluation of the diagnostic and prognostic value of plasma D-dimer for abdominal aortic aneurysm. Eur Heart J. 2011;32(3):354–64.CrossRefPubMed
64.
65.
Clancy P, et al. Assessment of a serum assay for quantification of abdominal aortic calcification. Arterioscler Thromb Vasc Biol. 2006;26(11):2574–6.CrossRefPubMed
66.
67.
Biros E, et al. Differential gene expression in the proximal neck of human abdominal aortic aneurysm. Atherosclerosis. 2014;233(1):211–8.CrossRefPubMed
68.
Biros E, et al. microRNA profiling in patients with abdominal aortic aneurysms: the significance of miR-155. Clin Sci (Lond). 2014;126(11):795–803.CrossRef
69.
Chong PF, et al. The intermittent claudication questionnaire: a patient-assessed condition-specific health outcome measure. J Vasc Surg. 2002;36(4):764–71. discussion 863–4.CrossRefPubMed
70.
Bingham SA, et al. Comparison of dietary assessment methods in nutritional epidemiology: weighed records v. 24 h recalls, food-frequency questionnaires and estimated-diet records. Br J Nutr. 1994;72(4):619–43.CrossRefPubMed
71.
Golledge J, et al. Body mass index is inversely associated with mortality in patients with peripheral vascular disease. Atherosclerosis. 2013;229(2):549–55.CrossRefPubMed
72.
Golledge J, et al. Association of chronic kidney disease categories defined with different formulae with major adverse events in patients with peripheral vascular disease. Atherosclerosis. 2014;232(2):289–97.CrossRefPubMed
73.
Golledge J, et al. Association of impaired fasting glucose, diabetes and their management with the presentation and outcome of peripheral artery disease: a cohort study. Cardiovasc Diabetol. 2014;13:147.CrossRefPubMedPubMedCentral
74.
Burton NW, et al. Efficacy of brief behavioral counselling by allied health professionals to promote physical activity in people with peripheral arterial disease (BIPP): study protocol for a multi-center randomized controlled trial. BMC Public Health. 2016;16(1):1148.CrossRefPubMedPubMedCentral
75.
Morris DR, et al. TElmisartan in the management of abDominal aortic aneurYsm (TEDY): the study protocol for a randomized controlled trial. Trials. 2015;16:274.CrossRefPubMedPubMedCentral
76.
Rowbotham SE. Fenofibrate in the management of AbdoMinal aortic anEurysm (FAME)-2: the study protocol for a multi-centre, randomised, placebo-controlled trial. Int J Clin Trials. 2016;3:217–24.CrossRef
77.
Rowbotham SE, et al. Fenofibrate in the management of AbdoMinal aortic anEurysm (FAME): study protocol for a randomised controlled trial. Trials. 2017;18(1):1.CrossRefPubMedPubMedCentral
78.
79.
Meijer CA, et al. Doxycycline for stabilization of abdominal aortic aneurysms: a randomized trial. Ann Intern Med. 2013;159(12):815–23.CrossRefPubMed
Metadata
Title
Inositol in the MAnaGemENt of abdominal aortic aneurysm (IMAGEN): study protocol for a randomised controlled trial
Authors
Sophie E. Rowbotham
Jenna L. Pinchbeck
Georgina Anderson
Bernie Bourke
Michael Bourke
T. Christian Gasser
Rene Jaeggi
Jason S. Jenkins
Corey S. Moran
Susan K. Morton
Christopher M. Reid
Ramesh Velu
Lisan Yip
Joseph V. Moxon
Jonathan Golledge
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Trials / Issue 1/2017
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/s13063-017-2304-x

Other articles of this Issue 1/2017

Trials 1/2017 Go to the issue

Review

Reporting quality of randomized controlled trials in patients with HIV on antiretroviral therapy: a systematic review

Study protocol

School-based cognitive behavioral interventions for anxious youth: study protocol for a randomized controlled trial

Study protocol

Neoadjuvant everolimus plus letrozole versus fluorouracil, epirubicin and cyclophosphamide for ER-positive, HER2-negative breast cancer: study protocol for a randomized pilot trial

Study protocol

Research Exploring Physical Activity in Care Homes (REACH): study protocol for a randomised controlled trial

Study protocol

The TECH@HOME study, a technological intervention to reduce caregiver burden for informal caregivers of people with dementia: study protocol for a randomized controlled trial

Study protocol

Perineural local anaesthetic catheter after major lower limb amputation trial (PLACEMENT): study protocol for a randomised controlled pilot study