Hypoproteic Diet in Acromegaly

Study Overview
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Brief Summary
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Since protein and AAs are master regulator of GH and IGF-I secretion, we hypothesized that a low protein diet could reduce GH and IGF-I levels in acromegalic patients in addition to conventional therapy. Furthermore, we aim to explore metabolomic, microbiota, and micro-vesicle fingerprints of GH hypersecretion during conventional therapy and after a low protein diet

Detailed Description
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Nutrients are crucial modifiers of the GH/IGF-I axis. In particular, a close cross-talk between proteins and amino acids (AAs) and GH/IGF-I secretion exists. Both AAs and proteins affect GH secretion. AAs stimulate GH secretion upon oral administration, with different potency among studies, being the combination of arginine and lysine the most powerful. Soy proteins also stimulate GH secretion when ingested either as hydrolysed proteins or free AAs. Furthermore, the acute GH response to AAs ingestion may be influenced by the daily amount of dietary protein/AAs consumption: diets high in proteins apparently increase basal GH levels. AAs and proteins have a positive effect on IGF-I secretion as well. In general, high levels of proteins, especially animal and dairy proteins, and consumption of branched chain amino acids (BCAAs) increase serum IGF-I levels. Considering pathological GH conditions, metabolomic analysis of acromegalic patients suggests that the main metabolic fingerprint of GH hypersecretion is a reduction in BCAAs, related to the disease activity. Moreover, there is evidence that GH, rather than IGF-I, is the main mediator of such metabolic fingerprint, which may be related to increased uptake of BCAAs by the muscles, increased gluconeogenesis, and raised consumption of BCAAs. Thus, in acromegaly, a tailored diet is a further strategy that may contribute to blunt GH/IGF-I secretion. Indeed, some authors recently suggested that personalized or precision nutrition in some conditions and diseases could have an impact on their phenotype, combining dietary recommendations with individual's genetic makeup, metabolic and microbiome characteristics, and environment. However, studies on precision nutrition in acromegaly are still in a neonatal era.

Official Title
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Deciphering the Role of a Low Protein Diet in Disease Control in Acromegalic Patients

Conditions
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Acromegaly

Intervention / Treatment
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* Other: Usual clinical practice + hypoproteic diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18/65 Diagnosis of Acromegaly In therapy with somatostatin analogues Exclusion Criteria: pregnancy or lactation alchool or drugs abuse cancer Hematological diseases

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Acromegalic adult in therapy with somatostatin analogues<br>Patients will continue the usual medical outpatient visits cadency and will keep the same pharmacological therapy throughout the whole duration of the study. Drugs have to include somatostatin analogues. At the same time, patients will be trained by an expert dietician in the habit of an isocaloric and hypoproteic diet and will come back at 2,4,6 and 8 weeks after T0 for all the necessary study assessments and compliance checking. | Other: Usual clinical practice + hypoproteic diet<br>* Diet will be composed by: energy equal to daily energy expenditure (estimated by indirect calorimetry * physical activity factor) fats 28-35% carbohydrates 50-60% proteins 0,7-0,8g/kg of body weight 10-13% Diet will be given to the patient after the first visit and the study will start once the patient begins the diet.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in disease related hormones | Variation of GH, IGF-1, IGFBP1, IGFBP3 hormones | Change from Baseline GH, IGF-1, IGFBP1, IGFBP3 blood levels at 15 days, 30 days, 45 days, 60 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in weight | Variation of body weight assessed through body mass index change (BMI)(kg/m2) | Change from Baseline BMI at 15 days, 30 days, 45 days, 60 days | 
| Change in body circumferences | Variation of body circumferences (waist, hips) | Change from Baseline circumferences at 15 days, 30 days, 45 dyas, 60 days | 
| Change in metabolic control | Change of cardio-metabolic risk factors: lipid profile | Change from Baseline lipid profile at 15 days, 30 days, 45 days, 60 days | 
| Change in metabolic control | Change of cardio-metabolic risk factors: insulin resistance (HOMA-IR) | Change from Baseline lipid profile at 60 days | 
| Change in kidney profile | Variation of serum creatinin | Change from Baseline Serum Creatinin at 15 days, 30 days, 45 days, 60 days | 
| Change in liver profile | Variation of liver markers(AST, ALT, GGT) | Change from Baseline Serum Creatinin at 15 days, 30 days, 45 days, 60 days | 
| Change in uric acid | Variation of uric acid in blood through enzymatic determination | Change from Baseline uric acid in blood at 15 days, 30 days, 45 days, 60 days | 
| Change in body composition | Change of body composition (fat mass %) (BIVA) | Change from Baseline fat mass% at 60 days | 
| Change in body composition | Change of body composition (fat mass %) (DXA) | Change from Baseline fat mass% at 60 days | 
| Change in blood count | Variation of blood count | Change from Baseline blood count at 15 days, 30 days, 45 days, 60 days | 
| Change in microbiota | Variation of prevalence of microbiota phyla through DNA sequencing of stools | Change from Baseline of prevalence of microbiota phyla at 15, 30 days, 45 days, 60 days | 
| Change in omics profile | Variation of lipidomic profile of stools through liquid and gas chromatography | Change from Baseline omic profile of stools at 15, 30 days, 45 days, 60 days | 
| Change in omics profile | Variation of proteomic profile of stools through liquid and gas chromatography | Change from Baseline omic profile of stools at 15, 30 days, 45 days, 60 days | 
| Change in microvesicles | Variation of urinary microvesicles levels | Change from Baseline microvesicles levels at 15, 30 days, 45 days, 60 days | 
| Change in microvesicles | Variation of serum microvesicles levels | Change from Baseline microvesicles levels s at 15, 30 days, 45 days, 60 days | 
| Change in basal metabolic rate | Variation of basal metabolic rate (kcal) | Change from Baseline basal metabolic rate at 60 days |