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

NCT00553852 | Completed Phase 3 DMC

• 1 other identifier: NeuroendoUnit-5
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Obesity; GHD

Keywords

Very Severe Obesity; Body Composition; GH deficiency; IGF-I; LASGB; GH therapy

Outcome Measures

Primary Outcomes (1)

• Fat mass (%), free fat mass (%), percent decrease of fat mass.

  6 months

Secondary Outcomes (2)

• Lipid profile

  6 months

• Fasting plasma glucose and insulin

  6 months

Study Arms (2)

1

EXPERIMENTAL

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.

Drug: Recombinant GH Saizen (Merck-Serono)

2

PLACEBO COMPARATOR

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).

Drug: Recombinant GH Saizen (Merck-Serono)

Interventions

Recombinant GH Saizen (Merck-Serono) DRUG

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.

1; 2

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age between 18-50 yrs
• Normal glucose tolerance during standard oral glucose tolerance test (OGTT)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Federico II University: lead

Study Sites (1)

Department of Molecular and Clinical Endocrinology and Oncology Federico II University

Naples, 80131, Italy

Location

Related Publications (27)

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  PMID: 16840832 RESULT

• 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.

  PMID: 19066295 DERIVED

MeSH Terms

Conditions

Obesity; Dwarfism, Pituitary

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Dwarfism; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Bone Diseases, Endocrine; Hypopituitarism; Pituitary Diseases; Hypothalamic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Endocrine System Diseases

Study Officials

• Annamaria Colao, MD, PhD

  Department of Molecular and Clinical Endocrinology and Oncology Federico II University of Naples

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: October 31, 2007
• First Posted: November 6, 2007
• Study Start: July 1, 2007
• Primary Completion: January 1, 2008
• Study Completion: March 1, 2008
• Last Updated: March 28, 2008

Record last verified: 2008-03

Locations

IT (1)