Evaluation of GH/IGF-I Axis and of Replacement GH Therapy After Bariatric Surgery in Patients With Very Severe Obesity: Relationships With Body Composition
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Fat mass (%), free fat mass (%), percent decrease of fat mass.
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: Recombinant GH Saizen (Merck-Serono) (Drug)
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).
干预措施: Recombinant GH Saizen (Merck-Serono) (Drug)
结局指标
主要结局
Fat mass (%), free fat mass (%), percent decrease of fat mass.
时间窗: 6 months
次要结局
- Lipid profile(6 months)
- Fasting plasma glucose and insulin(6 months)