Cardiovascular Risk Factors and LCH in Adults
Recruitment status was Recruiting
|First Received Date ICMJE||June 6, 2007|
|Last Updated Date||June 7, 2007|
|Start Date ICMJE||September 2005|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE||Not Provided|
|Original Primary Outcome Measures ICMJE||Not Provided|
|Change History||Complete list of historical versions of study NCT00483925 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE||Not Provided|
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Cardiovascular Risk Factors and LCH in Adults|
|Official Title ICMJE||CARDIOVASCULAR RISK FACTORS IN ADULT PATIENTS WITH MULTISYSTEM LANGERHANS-CELL HISTIOCYTOSIS: EVIDENCE OF GLUCOSE METABOLISM ABNORMALITIES|
Langerhans-cell histiocytosis (LCH) is a rare disease with features of chronic inflammation and hypopituitarism, conditions associated with increased risk of cardiovascular diseases.
Objective: To investigate glucose and lipid metabolism, insulin resistance, structural arterial and functional endothelial properties in patients with multisystem LCH in a prospective, observational study.
Interventions:Cardiovascular risk factors: arterial blood pressure, lipid profile, mathematical indices of insulin resistance (IR), intima media thickness, brachial artery flow mediated dilatation, dynamic indices of IR, pituitary function and C-reactive protein will be estimated in patients with LCH and in a control group matched for gender, age, BMI and smoking habits.
CARDIOVASCULAR RISK FACTORS IN ADULT PATIENTS WITH MULTISYSTEM LANGERHANS-CELL HISTIOCYTOSIS: EVIDENCE OF ABNORMALITIES OF CARBOHYDRATE METABOLISM
Langerhans cell histiocytosis (LCH) is a rare disease, usually affecting children although it has recently increasingly been recognized in adults with a prevalence of approximately 1/560.000 cases ( , ). LCH is characterized by the aberrant proliferation of dendritic cells of the monocyte-macrophage system that resemble normal epidermal Langerhans’ cells. These cells can infiltrate many sites of the body leading to either localized lesions or widespread systemic disease. Although LCH has been shown to be a clonal disorder ( ) it also exhibits features of an inflammatory disease, as altered expression of cytokines and cellular adhesion molecules important for the migration and homing of Langerhans cell has been documented ( , ). In addition, LCH shows a particular predilection for hypothalamo-pituitary axis (HPA) involvement leading to diabetes insipidus and/ or anterior pituitary dysfunction in 15–50% and 5–20%, of patients respectively (3, , , ). These percentages may be higher in adult patients with multisystem involvement, being 94% and 59% respectively ( ).
The ongoing inflammatory process and the presence of hypopituitarism are considered to be two independent risk factors for cardiovascular diseases probably through the induction of insulin resistance (IR) ( , , ). The various therapies used for the treatment of multisystem LCH, chemotherapy, radiotherapy and particularly glucocorticoids, may also adversely affect the cardiovascular system mostly through IR ( , ). It is therefore possible that patients with LCH represent a group at higher risk for cardiovascular diseases through the additive effect of a number of different contributing mechanisms known to induce IR. Insulin resistance besides producing an adverse metabolic profile can also lead to endothelial dysfunction and early vascular disease ( ). Early vascular disease can be detected by non-invasive surrogate markers, such as intima-media thickness (IMT) for vascular structure properties and flow-mediated vasodilatation (FMD) for vascular functional properties ( , , ). Carotid IMT is considered an established marker for early atherosclerotic disease and predictor of future cardiovascular events (16) whereas brachial artery FMD has been correlated with coronary endothelial function, a well-known predictor of future cardiovascular events (18).
Main outcome measures: Cardiovascular risk factors assessment were estimated in patients with LCH and compared to controls; the effect of hypopituitarism, disease activity and/ or treatment were determined.
SUBJECTS AND METHODS All patients have to fulfil the diagnostic criteria for “definitive diagnosis” of LCH ( ). Matched to sex, age, and BMI healthy individuals, in good health and not receiving any medication known to affect carbohydrate, sex hormone metabolism, and/or endothelial function for at least 3 months prior have also to be recruited for the study.
Clinical data of the patients as well as hormonal and imaging assessment will be registered.
All subjects do not have participate in strenuous physical activities and have to be on a balanced isocaloric diet for at least 4 weeks prior to the study. Current smokers will be asked not to smoke one day before the hemodynamic study.
Cardiovascular risk factors assessment:
Clinical cardiovascular risk:
The metabolic study of all patients will be performed after a 10h overnight fasting:
Inflammatory index C-reactive protein (CRP) measurement. References Baumgartner I, von Hochstetter A, Baumert B, Luetolf U, Follath F 1997 Med Pediatr Oncol 28:9-14
W Wheatcroft SB, Williams IL, Shah AM, Kearney MT 2003 Pathophysiological implications of insulin resistance on vascular endothelial function Diabet Med 20:255-268
Hodis HN, Mack WJ, LaBree L, Selzer RH, Liu CR, Liu CH, Azen SP 1998 The role of carotid arterial intima-media thickness in predicting clinical coronary events.
Ann Intern Med 128:262-269
Schachinger V, Britten MB, Zeiher AM 2000 Prognostic impact of coronary vasodilator dysfunction on adverse long-term outcome of coronary heart disease.
Anderson TJ, Uehata A, Gerhard MD, Meredith IT, Knab S, Delagrange D, Lieberman EH, Ganz P, Creager MA, Yeung AC, et al 1995 Close relation of endothelial function in the human coronary and peripheral circulations J Am Coll Cardiol 26:1235-1241
Arico M, Girschikofsky M, Genereau T, Klersy C, McClain K, Grois N, Emile JF, Lukina E, De Juli E, Danesino C 2003 Langerhans cell histiocytosis in adults. Report from the International Registry of the Histiocyte Society Eur J Cancer 39:2341-2348
Legro RS, Finegood D, Dunaif A 1998 A fasting glucose to insulin ratio is a useful measure of insulin sensitivity in women with polycystic ovary syndrome J Clin Endocrinol Metab 83:2694-2698
Bergman RN, Prager R, Volund A, Olefsky JM 1987 Equivalence of the insulin sensitivity index in man derived by the minimal model method and the euglycemic glucose clamp J Clin Invest 79:790-800
Katz A, Nambi SS, Mather K, Baron AD, Follmann DA, Sullivan G, Quon MJ 2000 Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans J Clin Endocrinol Metab 85:2402-2410
Matsuda M, DeFronzo RA 1999 Insulin sensitivity indices obtained from oral glucose tolerance testing. Comparison with the euglycemic insulin clamp Diabetes Care 22:1462-1470
Stumvoll M, Mitrakou A, Pimenta W, Jenssen T, Yki-Jarvinen H, Van Haeften T, Renn W, Gerich J Use of the oral glucose tolerance test to assess insulin release and insulin sensitivity Diabetes Care 295–301
Alexandraki K, Protogerou A, Papaioannou TG, Piperi C, Mastorakos G, Lekakis J, Panidis D, Diamanti-Kandarakis E 2006 Early Microvascular and Macrovascular Dysfunction is not Accompanied by Structural Injury in Polycystic Ovary Syndrome. HORMONES (Athens Greece) 5:126-136
|Study Type ICMJE||Observational|
|Study Design ICMJE||Observational Model: Case Control
Primary Purpose: Screening
Time Perspective: Longitudinal
|Target Follow-Up Duration||Not Provided|
|Sampling Method||Not Provided|
|Study Population||Not Provided|
|Condition ICMJE||Histiocytosis, Langerhans-Cell|
|Intervention ICMJE||Not Provided|
|Study Group/Cohort (s)||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Recruiting|
|Enrollment ICMJE||Not Provided|
|Completion Date||Not Provided|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
|Ages||18 Years and older|
|Accepts Healthy Volunteers||Yes|
|Location Countries ICMJE||Greece|
|NCT Number ICMJE||NCT00483925|
|Other Study ID Numbers ICMJE||ES 511|
|Has Data Monitoring Committee||No|
|Responsible Party||Not Provided|
|Study Sponsor ICMJE||Laikon General District Hospital, Athens|
|Collaborators ICMJE||Not Provided|
|Information Provided By||Laikon General District Hospital, Athens|
|Verification Date||June 2007|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP