- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00553852
Replacement GH Therapy After Bariatric Surgery in Patients With Very Severe Obesity (GH&LASGB)
Evaluation of GH/IGF-I Axis and of Replacement GH Therapy After Bariatric Surgery in Patients With Very Severe Obesity: Relationships With Body Composition
Study Overview
Status
Intervention / Treatment
Detailed Description
The objectives of the study are:
- To evaluate the GH/GF-I status is correlation with body composition in very severe obese patients. IGF-I levels were classified as deficient when the standard deviation score from the mean was <-2 for age and gender.
- To evaluate the efficacy of a medical treatment with recombinant GH replacement therapy in very severe obese patients after LASGB on the Fat mass (%), free fat mass (%), percent decrease of fat mass. In line with GHD diagnosis, obese patients with persistent GHD after bariatric surgery will be randomized to be treated with or without recombinant GH therapy with replacement doses, in addition to the controlled trial of dietary management, as routinely performed after LASGB.
Study protocol The study protocol includes two different arms: a correlation observational longitudinal open study (Phase I), and a treatment study (Phase II).
PHASE I: In the correlation study a clinical, biochemical and instrumental evaluation will be performed in 20-30 patients with very severe obesity (grade III) with GHD followed-up in a multi-disciplinary approach at the Unit of Endocrinology of the Departments of Molecular and Clinical Endocrinology and Oncology and at the Physiology Nutrition Unit of the Department of Neuroscience and the Department of Surgery of "S. Giovanni Bosco" Hospital of Naples, according to the current criteria of the National Institute of Health (27). The clinical examination will focus on the GH/IGF-I status effects on body composition changes before and after LASGB. The clinical examination will determine anthropometric indexes (weight, height, BMI, waist circumference). The biochemical evaluation will include the measurement of lipid profile, fasting plasma glucose and insulin, liver test function, FT3, FT4, GHRH + Arginine test to detect GHD, plasma IGF-I levels. The instrumental evaluation will include DEXA Total Body and bioimpedance analysis to determine body composition, and liver ultrasounds.
PHASE II: In the medical treatment protocol very severe obese patients with persistent GHD after LASGB will be inclosed. Starting from 15-day, GHD patients were re-evaluated by GHRH + Arginine test. After evaluation, the patients with persistent GHD will be randomized to be treated with Recombinant GH replacement therapy (Group A: Recombinant GH replacement therapy at the initial dose 0.15-0.30 mg/die; dose adjustment will be made according to IGF-I levels; Group B: no GH treatment). In both subgroups, the diet will arranged to fit an energy intake of 5.7 MJ/day (55% carbohydrate, 25% fat, 20% protein, 30 g fiber) and a moderate-intensity activity (brisk walking for 30-45 min/day) will be encouraged.
The evaluation of medical treatment efficacy will be based on the analysis of changes in anthropometric indexes, IGF-I levels, liver function test, body composition assessed by DEXA Total Body and bioimpedance analysis, liver ultrasounds. At 3 and 6 months, the patients of both subgroups A and B will be clinically re-evaluated, plasma samples for metabolic, liver function tests, and endocrine profile will be obtained, body composition and liver ultrasounds will be determined. At the end of the 6-months period of treatment and observation, the GH response to a subsequent GHRH + Arginine will be re-tested to confirm or to exclude GHD. All the patients with persistent GHD will continue recombinant GH therapy.
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
-
-
-
Naples, Italy, 80131
- Department of Molecular and Clinical Endocrinology and Oncology Federico II University
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Age between 18-50 yrs
- Normal glucose tolerance during standard oral glucose tolerance test (OGTT)
- Inclusion criteria for bariatric surgery proposed by the 1991 National Institutes of Health Consensus Development Panel Report.
Exclusion Criteria:
- Liver or renal failure, cancer, acute or chronic inflammatory diseases
- Chronic treatment with any type of medications
- organic pituitary deficiency
- Bulimia Nervosa of the DSM-IV
- Ulcers or malignancies excluded by oesophagus-gastro-duodenoscopy.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 1
The clinical examination will determine anthropometric indexes (weight, height, BMI, waist circumference).
The biochemical evaluation will include the measurement of lipid profile, fasting plasma glucose and insulin, liver test function, FT3, FT4, GHRH + Arginine test to detect GHD, plasma IGF-I levels.
The instrumental evaluation will include DEXA Total Body and bioimpedance analysis to determine body composition, and liver ultrasounds.
|
Treatment will start at the initial dose 0.15-0.30
mg/day; dose adjustment will be performed according to IGF-I levels.
The duration of medical treatment is 6 months.
|
Placebo Comparator: 2
PHASE II: In the medical treatment protocol very severe obese patients with persistent GHD after LASGB will be inclosed.
Starting from 15-day, GHD patients were re-evaluated by GHRH + Arginine test.
After evaluation, the patients with persistent GHD will be randomized to be treated with Recombinant GH replacement therapy (Group A: Recombinant GH replacement therapy at the initial dose 0.15-0.30
mg/die; dose adjustment will be made according to IGF-I levels; Group B: no GH treatment).
|
Treatment will start at the initial dose 0.15-0.30
mg/day; dose adjustment will be performed according to IGF-I levels.
The duration of medical treatment is 6 months.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Fat mass (%), free fat mass (%), percent decrease of fat mass.
Time Frame: 6 months
|
6 months
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Lipid profile
Time Frame: 6 months
|
6 months
|
Fasting plasma glucose and insulin
Time Frame: 6 months
|
6 months
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Annamaria Colao, MD, PhD, Department of Molecular and Clinical Endocrinology and Oncology Federico II University of Naples
Publications and helpful links
General Publications
- DeMaria EJ. Bariatric surgery for morbid obesity. N Engl J Med. 2007 May 24;356(21):2176-83. doi: 10.1056/NEJMct067019. No abstract available.
- Yusuf S, Hawken S, Ounpuu S, Dans T, Avezum A, Lanas F, McQueen M, Budaj A, Pais P, Varigos J, Lisheng L; INTERHEART Study Investigators. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet. 2004 Sep 11-17;364(9438):937-52. doi: 10.1016/S0140-6736(04)17018-9.
- Groves T. Pandemic obesity in Europe. BMJ. 2006 Nov 25;333(7578):1081. doi: 10.1136/bmj.39038.449769.BE. Epub 2006 Nov 17.
- Renehan AG, Frystyk J, Flyvbjerg A. Obesity and cancer risk: the role of the insulin-IGF axis. Trends Endocrinol Metab. 2006 Oct;17(8):328-36. doi: 10.1016/j.tem.2006.08.006. Epub 2006 Sep 7.
- Kuzmak LI. A Review of Seven Years' Experience with Silicone Gastric Banding. Obes Surg. 1991 Dec;1(4):403-408. doi: 10.1381/096089291765560809.
- Angrisani L, Lorenzo M, Esposito G, Romano G, Puzziello A, Belfiore A, Santoro T, Roina G, Petito A, Falconi C, Tesauro B. Laparoscopic adjustable silicone gastric banding: preliminary results of the University of Naples experience. Obes Surg. 1997 Feb;7(1):19-21. doi: 10.1381/096089297765556178.
- Ravussin E, Burnand B, Schutz Y, Jequier E. Energy expenditure before and during energy restriction in obese patients. Am J Clin Nutr. 1985 Apr;41(4):753-9. doi: 10.1093/ajcn/41.4.753.
- Sergi G, Lupoli L, Busetto L, Volpato S, Coin A, Bertani R, Calliari I, Berton A, Enzi G. Changes in fluid compartments and body composition in obese women after weight loss induced by gastric banding. Ann Nutr Metab. 2003;47(3-4):152-7. doi: 10.1159/000070038.
- Savastano S, Valentino R, Belfiore A, De Luca N, de Alteriis A, Orio F Jr, Palomba S, Villani AM, Falconi C, Lupoli G, Lombardi G. Early carotid atherosclerosis in normotensive severe obese premenopausal women with low DHEA(S). J Endocrinol Invest. 2003 Mar;26(3):236-43. doi: 10.1007/BF03345163. Erratum In: J Endocrinol Invest. 2003 May;26(5):IV. Falcone C [corrected to Falconi C].
- Savastano S, Belfiore A, Guida B, Angrisani L, Orio F Jr, Cascella T, Milone F, Micanti F, Saldalamacchia G, Lombardi G, Colao A. Role of dehydroepiandrosterone sulfate levels on body composition after laparoscopic adjustable gastric banding in pre-menopausal morbidly obese women. J Endocrinol Invest. 2005 Jun;28(6):509-15. doi: 10.1007/BF03347238.
- Richelsen B, Pedersen SB, Kristensen K, Borglum JD, Norrelund H, Christiansen JS, Jorgensen JO. Regulation of lipoprotein lipase and hormone-sensitive lipase activity and gene expression in adipose and muscle tissue by growth hormone treatment during weight loss in obese patients. Metabolism. 2000 Jul;49(7):906-11. doi: 10.1053/meta.2000.6738.
- Umpleby AM, Russell-Jones DL. The hormonal control of protein metabolism. Baillieres Clin Endocrinol Metab. 1996 Oct;10(4):551-70. doi: 10.1016/s0950-351x(96)80711-7.
- Maccario M, Grottoli S, Procopio M, Oleandri SE, Rossetto R, Gauna C, Arvat E, Ghigo E. The GH/IGF-I axis in obesity: influence of neuro-endocrine and metabolic factors. Int J Obes Relat Metab Disord. 2000 Jun;24 Suppl 2:S96-9. doi: 10.1038/sj.ijo.0801289.
- Garcia-Galiano D, Sanchez-Garrido MA, Espejo I, Montero JL, Costan G, Marchal T, Membrives A, Gallardo-Valverde JM, Munoz-Castaneda JR, Arevalo E, De la Mata M, Muntane J. IL-6 and IGF-1 are independent prognostic factors of liver steatosis and non-alcoholic steatohepatitis in morbidly obese patients. Obes Surg. 2007 Apr;17(4):493-503. doi: 10.1007/s11695-007-9087-1.
- Santini F, Giannetti M, Mazzeo S, Fierabracci P, Scartabelli G, Marsili A, Valeriano R, Pucci A, Anselmino M, Zampa V, Vitti P, Pinchera A. Ultrasonographic evaluation of liver volume and the metabolic syndrome in obese women. J Endocrinol Invest. 2007 Feb;30(2):104-10. doi: 10.1007/BF03347407.
- Molitch ME, Clemmons DR, Malozowski S, Merriam GR, Shalet SM, Vance ML; Endocrine Society's Clinical Guidelines Subcommittee, Stephens PA. Evaluation and treatment of adult growth hormone deficiency: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2006 May;91(5):1621-34. doi: 10.1210/jc.2005-2227. Epub 2006 Apr 24. Erratum In: J Clin Endocrinol Metab. 2021 Jun 16;106(7):e2849.
- Colao A, Cerbone G, Pivonello R, Aimaretti G, Loche S, Di Somma C, Faggiano A, Corneli G, Ghigo E, Lombardi G. The growth hormone (GH) response to the arginine plus GH-releasing hormone test is correlated to the severity of lipid profile abnormalities in adult patients with GH deficiency. J Clin Endocrinol Metab. 1999 Apr;84(4):1277-82. doi: 10.1210/jcem.84.4.5605.
- Colao A, Di Somma C, Pivonello R, Loche S, Aimaretti G, Cerbone G, Faggiano A, Corneli G, Ghigo E, Lombardi G. Bone loss is correlated to the severity of growth hormone deficiency in adult patients with hypopituitarism. J Clin Endocrinol Metab. 1999 Jun;84(6):1919-24. doi: 10.1210/jcem.84.6.5742.
- Colao A, Di Somma C, Cuocolo A, Filippella M, Rota F, Acampa W, Savastano S, Salvatore M, Lombardi G. The severity of growth hormone deficiency correlates with the severity of cardiac impairment in 100 adult patients with hypopituitarism: an observational, case-control study. J Clin Endocrinol Metab. 2004 Dec;89(12):5998-6004. doi: 10.1210/jc.2004-1042.
- Salomon F, Cuneo RC, Hesp R, Sonksen PH. The effects of treatment with recombinant human growth hormone on body composition and metabolism in adults with growth hormone deficiency. N Engl J Med. 1989 Dec 28;321(26):1797-803. doi: 10.1056/NEJM198912283212605.
- Vance ML, Mauras N. Growth hormone therapy in adults and children. N Engl J Med. 1999 Oct 14;341(16):1206-16. doi: 10.1056/NEJM199910143411607. No abstract available.
- Amato G, Mazziotti G, Di Somma C, Lalli E, De Felice G, Conte M, Rotondi M, Pietrosante M, Lombardi G, Bellastella A, Carella C, Colao A. Recombinant growth hormone (GH) therapy in GH-deficient adults: a long-term controlled study on daily versus thrice weekly injections. J Clin Endocrinol Metab. 2000 Oct;85(10):3720-5. doi: 10.1210/jcem.85.10.6881.
- Johannsson G, Marin P, Lonn L, Ottosson M, Stenlof K, Bjorntorp P, Sjostrom L, Bengtsson BA. Growth hormone treatment of abdominally obese men reduces abdominal fat mass, improves glucose and lipoprotein metabolism, and reduces diastolic blood pressure. J Clin Endocrinol Metab. 1997 Mar;82(3):727-34. doi: 10.1210/jcem.82.3.3809.
- Albert SG, Mooradian AD. Low-dose recombinant human growth hormone as adjuvant therapy to lifestyle modifications in the management of obesity. J Clin Endocrinol Metab. 2004 Feb;89(2):695-701. doi: 10.1210/jc.2003-031264.
- NIH conference. Gastrointestinal surgery for severe obesity. Consensus Development Conference Panel. Ann Intern Med. 1991 Dec 15;115(12):956-61.
- Savastano S, Di Somma C, Belfiore A, Guida B, Orio F Jr, Rota F, Savanelli MC, Cascella T, Mentone A, Angrisani L, Lombardi G, Colao A. Growth hormone status in morbidly obese subjects and correlation with body composition. J Endocrinol Invest. 2006 Jun;29(6):536-43. doi: 10.1007/BF03344144.
- Savastano S, Di Somma C, Angrisani L, Orio F, Longobardi S, Lombardi G, Colao A. Growth hormone treatment prevents loss of lean mass after bariatric surgery in morbidly obese patients: results of a pilot, open, prospective, randomized, controlled study. J Clin Endocrinol Metab. 2009 Mar;94(3):817-26. doi: 10.1210/jc.2008-1476. Epub 2008 Dec 9.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- NeuroendoUnit-5
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