Adipokines as Predictors of the Metabolic Syndrome in ALL Survivors

• ClinicalTrials.gov Identifier: NCT00566566
• Recruitment Status: Unknown
• First Posted: December 3, 2007
• Last Update Posted: December 3, 2007
• Sponsor: Sheba Medical Center
• Information provided by: Sheba Medical Center

Study Description

Brief Summary:

Background: Acute Lymphoblastic Leukemia (ALL) is the most common malignancy in children. It accounts for 25% of all childhood cancers. Peak incidence occurs between 2 to 5 years of age. Modern treatment regimens have improved cure rates from virtually zero (in the 1950's) to current overall survival rates of approximately 80%.The high survival rates have introduced us to novel medical problems as a consequences of the different treatment regimens. No single treatment modality exists today but rather several treatment protocols are accepted worldwide. As such, the population of the childhood ALL survivors differ in their toxic exposure: cranial & spinal radiotherapy, intrathecal and/or systemic chemotherapy and bone marrow transplantation .As the survival rates grow, there are more young adult ALL survivors worldwide susceptible to these late effects of treatment.

Numerous reports have pointed out that this particular group is at increased risk to develop cardiovascular disease (CVD) and diabetes (MS). The metabolic syndrome, i.e hypertension, dyslipidemia, impaired glucose metabolism and obesity, occurs at a younger age than the general population.

Adipocytokines, mediators secreted by adipose tissue, play an important role in the regulation of carbohydrates and lipid metabolism.Changes in serum adipokine levels precede the clinical symptoms.

We aim to identify and assess prevalence of the MS in ALL survivors. We aim to characterize the population at risk to develop DM and CVD prior to overt clinical disease. Characterization will be done by measuring serum adipocytokines and inflammatory cytokine profiles .Biochemical characterization of the group at risk will enable us to intervene in the preventive stage in the future.

Condition or disease	Intervention/treatment
Leukemia; Metabolic Syndrome X	Other: sample without DNA

Study Design

• Study Type: Observational
• Estimated Enrollment: 150 participants
• Observational Model: Cohort
• Official Title: Adipocytokines as Predictors of the Metabolic Syndrome in Survivors of Childhood Acute Lymphoblastic Leukemia
• Study Start Date: January 2008
• Estimated Study Completion Date: December 2008

Groups and Cohorts

Group/Cohort	Intervention/treatment
1; ALL survivors 5 years after completion of treatment, during routine medical follow up	Other: sample without DNA; family history, anthropometric measurements and blood sampling

Outcome Measures

Biospecimen Retention:   Samples Without DNA

Serum leptin, resistin ,adiponectin ,CRP, PAI ,TNF-α, IL-6 will be taken as part of initial blood test screening in patients following an overnight fast. Adiponectin and leptin levels will be determined by RIA (Linco, St. Charles, MO), Insulin, will be determined by chemiluminescent immunometric method (Immulite 2000, Diagnostic Products Corporation, Los Angeles, CA).

Eligibility Criteria

• Ages Eligible for Study: 6 Years to 45 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

Hematoncological pediatric clinic

Criteria

Inclusion Criteria:

• ALL diagnosis
• five years after completion of treatment
• leukemia free during research

Exclusion Criteria:

• ongoing chemotherapy and radiotherapy

Contacts and Locations

Contacts

Contact: Bella Bielorai, MD; 972-3-5302692; Bella.Bielorai@sheba.health.gov.il

Sponsors and Collaborators

Sheba Medical Center

Investigators

• Principal Investigator: Yael Weintraub, MD; Tel Aviv University

More Information

Publications:

Eckel RH, Grundy SM, Zimmet PZ. The metabolic syndrome. Lancet. 2005 Apr 16-22;365(9468):1415-28. doi: 10.1016/S0140-6736(05)66378-7.

Alberti KG, Zimmet P, Shaw J; IDF Epidemiology Task Force Consensus Group. The metabolic syndrome--a new worldwide definition. Lancet. 2005 Sep 24-30;366(9491):1059-62. doi: 10.1016/S0140-6736(05)67402-8. No abstract available.

Cook S, Weitzman M, Auinger P, Nguyen M, Dietz WH. Prevalence of a metabolic syndrome phenotype in adolescents: findings from the third National Health and Nutrition Examination Survey, 1988-1994. Arch Pediatr Adolesc Med. 2003 Aug;157(8):821-7. doi: 10.1001/archpedi.157.8.821.

Taskinen M, Saarinen-Pihkala UM, Hovi L, Lipsanen-Nyman M. Impaired glucose tolerance and dyslipidaemia as late effects after bone-marrow transplantation in childhood. Lancet. 2000 Sep 16;356(9234):993-7. doi: 10.1016/S0140-6736(00)02717-3.

Gurney JG, Ness KK, Sibley SD, O'Leary M, Dengel DR, Lee JM, Youngren NM, Glasser SP, Baker KS. Metabolic syndrome and growth hormone deficiency in adult survivors of childhood acute lymphoblastic leukemia. Cancer. 2006 Sep 15;107(6):1303-12. doi: 10.1002/cncr.22120.

Mohn A, Di Marzio A, Capanna R, Fioritoni G, Chiarelli F. Persistence of impaired pancreatic beta-cell function in children treated for acute lymphoblastic leukaemia. Lancet. 2004 Jan 10;363(9403):127-8. doi: 10.1016/S0140-6736(03)15264-6.

Razzouk BI, Rose SR, Hongeng S, Wallace D, Smeltzer MP, Zacher M, Pui CH, Hudson MM. Obesity in survivors of childhood acute lymphoblastic leukemia and lymphoma. J Clin Oncol. 2007 Apr 1;25(10):1183-9. doi: 10.1200/JCO.2006.07.8709.

Kourti M, Tragiannidis A, Makedou A, Papageorgiou T, Rousso I, Athanassiadou F. Metabolic syndrome in children and adolescents with acute lymphoblastic leukemia after the completion of chemotherapy. J Pediatr Hematol Oncol. 2005 Sep;27(9):499-501. doi: 10.1097/01.mph.0000181428.63552.e9.

Oeffinger KC, Buchanan GR, Eshelman DA, Denke MA, Andrews TC, Germak JA, Tomlinson GE, Snell LE, Foster BM. Cardiovascular risk factors in young adult survivors of childhood acute lymphoblastic leukemia. J Pediatr Hematol Oncol. 2001 Oct;23(7):424-30. doi: 10.1097/00043426-200110000-00007.

Koerner A, Kratzsch J, Kiess W. Adipocytokines: leptin--the classical, resistin--the controversical, adiponectin--the promising, and more to come. Best Pract Res Clin Endocrinol Metab. 2005 Dec;19(4):525-46. doi: 10.1016/j.beem.2005.07.008.

Pui CH, Cheng C, Leung W, Rai SN, Rivera GK, Sandlund JT, Ribeiro RC, Relling MV, Kun LE, Evans WE, Hudson MM. Extended follow-up of long-term survivors of childhood acute lymphoblastic leukemia. N Engl J Med. 2003 Aug 14;349(7):640-9. doi: 10.1056/NEJMoa035091. Erratum In: N Engl J Med. 2003 Sep 25;349(13):1299.

• Responsible Party: Dr. Yael Weintraub, Sheba Medical Cener
• ClinicalTrials.gov Identifier: NCT00566566
• Other Study ID Numbers: SHEBA-07-4861-YW-CTIL
• First Posted: December 3, 2007
• Last Update Posted: December 3, 2007
• Last Verified: November 2007

Keywords provided by Sheba Medical Center:

adipocytokines; inflammatory markers; cardiovascular disease; diabetes mellitus; Leptin

Additional relevant MeSH terms:

Leukemia; Insulin Resistance; Metabolic Syndrome; Syndrome; Disease; Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases