Replacement GH Therapy After Bariatric Surgery in Patients With Very Severe Obesity

Obesity Clinical Trial

— GH&LASGB  

Official title:

Evaluation of GH/IGF-I Axis and of Replacement GH Therapy After Bariatric Surgery in Patients With Very Severe Obesity: Relationships With Body Composition

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00553852
• Other study ID #: NeuroendoUnit-5
• Status: Completed
• Phase: Phase 3
• First received: October 31, 2007
• Last updated: March 27, 2008
• Start date: July 2007
• Est. completion date: March 2008

Study information

• Verified date: March 2008
• Source: Federico II University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: Ethics CommitteeItaly: Ministry of HealthItaly: National Institute of Health
• Study type: Interventional

Clinical Trial Summary

Obesity and obesity-related diseases have reached epidemic proportions in Western countries (1-3). Laparoscopic-adjustable silicone gastric banding (LASGB) is a purely restrictive operation that determine effective weight loss without inducing malabsorption (4-6). However, also after LASGB body weight loss is almost invariably associated with Free Fat Mass (FFM) loss, and the relevance of the FFM contribution to total energy expenditure is well-known (7-8). Different endocrine axes are reported to affect FFM. We previously reported that low levels of DHEA-S, an adrenal steroid with controversial anti-adipogenic and anti-atherogenic effects, are increased after the massive and sustainable weight loss induced by LASGB in severely obese premenopausal women and correlated with the higher post-operative FFM (9-10). It is also well known that GH/IGF-I axis exerts relevant effects on FFM and that reduced GH levels might increase Fat Mass (FM) and reduce FFM (11,12). Morbidly obese patients have a reduced GH secretion, generally reversible after weight loss (13-14). In a recent study currently in press, we reported that a persistent deficiency in the GH/IGF-I axis in very obese females is associated to lower decrease in FM after LASGB. Low IGF-I plasma levels have also been reported to be independent prognostic factors of liver steatosis and non-alcoholic steatohepatitis in morbidly obese patients (15) and ultrasound- measured hepatic left lobe volume might represent a reliable tool for the evaluation of liver involvement in obesity (16). GH deficiency (GHD) in adult patients is associated with an increase in FM and a parallel decrease in FFM (17). The severity of GDH is correlated to cardiovascular risk, body composition abnormalities and bone loss, and decreased left ventricular ejection fraction (18-20). GH therapy has been demonstrated to be effective in normalizing body composition, with beneficial effects up to a 2-years follow-up period (21-24). GH therapy has also been reported to be effective in sparing FFM during weight loss in obese patients and metabolic syndrome (25,26). However, these studies have some limitations due to the duration of the treatment and the lack of a preliminary evaluation of the GH/IGF-I axis secretory status in obese patients before the GH therapy. At present there are no data on the evaluation of the GH/IGF-I status before and after bariatric surgery and the effectiveness of recombinant GH treatment in very severe obese patients.

Description:

The objectives of the study are:

1. 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.

2. 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: March 2008
• Est. primary completion date: January 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 50 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• GHD
• Obesity
• Obesity, Morbid

Intervention

Drug:
• Recombinant GH Saizen (Merck-Serono)
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.

Locations

Country	Name	City	State
Italy	Department of Molecular and Clinical Endocrinology and Oncology Federico II University	Naples

Sponsors (1)

Lead Sponsor	Collaborator
Federico II University

Country where clinical trial is conducted

Italy, 

References & Publications (26)

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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. — View Citation

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. — View Citation

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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;2 — View Citation

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* Note: There are 26 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Fat mass (%), free fat mass (%), percent decrease of fat mass.		6 months	No
Secondary	Lipid profile		6 months	Yes
Secondary	Fasting plasma glucose and insulin		6 months	Yes