IpoProAcro: Hypoproteic Diet in Acromegaly
Study Details
Study Description
Brief Summary
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
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Acromegalic adult in therapy with somatostatin analogues 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
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.
|
Outcome Measures
Primary Outcome Measures
- Change in disease related hormones [Change from Baseline GH, IGF-1, IGFBP1, IGFBP3 blood levels at 15 days, 30 days, 45 days, 60 days]
Variation of GH, IGF-1, IGFBP1, IGFBP3 hormones
Secondary Outcome Measures
- Change in weight [Change from Baseline BMI at 15 days, 30 days, 45 days, 60 days]
Variation of body weight assessed through body mass index change (BMI)(kg/m2)
- Change in body circumferences [Change from Baseline circumferences at 15 days, 30 days, 45 dyas, 60 days]
Variation of body circumferences (waist, hips)
- Change in metabolic control [Change from Baseline lipid profile at 15 days, 30 days, 45 days, 60 days]
Change of cardio-metabolic risk factors: lipid profile
- Change in metabolic control [Change from Baseline lipid profile at 60 days]
Change of cardio-metabolic risk factors: insulin resistance (HOMA-IR)
- Change in kidney profile [Change from Baseline Serum Creatinin at 15 days, 30 days, 45 days, 60 days]
Variation of serum creatinin
- Change in liver profile [Change from Baseline Serum Creatinin at 15 days, 30 days, 45 days, 60 days]
Variation of liver markers(AST, ALT, GGT)
- Change in uric acid [Change from Baseline uric acid in blood at 15 days, 30 days, 45 days, 60 days]
Variation of uric acid in blood through enzymatic determination
- Change in body composition [Change from Baseline fat mass% at 60 days]
Change of body composition (fat mass %) (BIVA)
- Change in body composition [Change from Baseline fat mass% at 60 days]
Change of body composition (fat mass %) (DXA)
- Change in blood count [Change from Baseline blood count at 15 days, 30 days, 45 days, 60 days]
Variation of blood count
- Change in microbiota [Change from Baseline of prevalence of microbiota phyla at 15, 30 days, 45 days, 60 days]
Variation of prevalence of microbiota phyla through DNA sequencing of stools
- Change in omics profile [Change from Baseline omic profile of stools at 15, 30 days, 45 days, 60 days]
Variation of lipidomic profile of stools through liquid and gas chromatography
- Change in omics profile [Change from Baseline omic profile of stools at 15, 30 days, 45 days, 60 days]
Variation of proteomic profile of stools through liquid and gas chromatography
- Change in microvesicles [Change from Baseline microvesicles levels at 15, 30 days, 45 days, 60 days]
Variation of urinary microvesicles levels
- Change in microvesicles [Change from Baseline microvesicles levels s at 15, 30 days, 45 days, 60 days]
Variation of serum microvesicles levels
- Change in basal metabolic rate [Change from Baseline basal metabolic rate at 60 days]
Variation of basal metabolic rate (kcal)
Eligibility Criteria
Criteria
Inclusion Criteria:
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Age 18/65
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Diagnosis of Acromegaly
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In therapy with somatostatin analogues
Exclusion Criteria:
-
pregnancy or lactation
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alchool or drugs abuse
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cancer
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Hematological diseases
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | : Italy Pediatric Endocrine Service of AOU Maggiore della Carità of Novara; SCDU of Pediatrics, Department of Health Sciences, University of Eastern Piedmont | Novara | Italy | 28100 |
Sponsors and Collaborators
- Azienda Ospedaliero Universitaria Maggiore della Carita
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
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- Beasley JM, Gunter MJ, LaCroix AZ, Prentice RL, Neuhouser ML, Tinker LF, Vitolins MZ, Strickler HD. Associations of serum insulin-like growth factor-I and insulin-like growth factor-binding protein 3 levels with biomarker-calibrated protein, dairy product and milk intake in the Women's Health Initiative. Br J Nutr. 2014 Mar 14;111(5):847-53. doi: 10.1017/S000711451300319X. Epub 2013 Oct 7.
- Caputo M, Pigni S, Agosti E, Daffara T, Ferrero A, Filigheddu N, Prodam F. Regulation of GH and GH Signaling by Nutrients. Cells. 2021 Jun 2;10(6). pii: 1376. doi: 10.3390/cells10061376. Review.
- Coopmans EC, Berk KAC, El-Sayed N, Neggers SJCMM, van der Lely AJ. Eucaloric Very-Low-Carbohydrate Ketogenic Diet in Acromegaly Treatment. N Engl J Med. 2020 May 28;382(22):2161-2162. doi: 10.1056/NEJMc1915808.
- Hoppe C, Udam TR, Lauritzen L, Mølgaard C, Juul A, Michaelsen KF. Animal protein intake, serum insulin-like growth factor I, and growth in healthy 2.5-y-old Danish children. Am J Clin Nutr. 2004 Aug;80(2):447-52.
- Levine ME, Suarez JA, Brandhorst S, Balasubramanian P, Cheng CW, Madia F, Fontana L, Mirisola MG, Guevara-Aguirre J, Wan J, Passarino G, Kennedy BK, Wei M, Cohen P, Crimmins EM, Longo VD. Low protein intake is associated with a major reduction in IGF-1, cancer, and overall mortality in the 65 and younger but not older population. Cell Metab. 2014 Mar 4;19(3):407-17. doi: 10.1016/j.cmet.2014.02.006.
- Li R, Ferreira MP, Cooke MB, La Bounty P, Campbell B, Greenwood M, Willoughby DS, Kreider RB. Co-ingestion of carbohydrate with branched-chain amino acids or L-leucine does not preferentially increase serum IGF-1 and expression of myogenic-related genes in response to a single bout of resistance exercise. Amino Acids. 2015 Jun;47(6):1203-13. doi: 10.1007/s00726-015-1947-8. Epub 2015 Mar 5.
- Romo Ventura E, Konigorski S, Rohrmann S, Schneider H, Stalla GK, Pischon T, Linseisen J, Nimptsch K. Association of dietary intake of milk and dairy products with blood concentrations of insulin-like growth factor 1 (IGF-1) in Bavarian adults. Eur J Nutr. 2020 Jun;59(4):1413-1420. doi: 10.1007/s00394-019-01994-7. Epub 2019 May 14.
- Sellini M, Fierro A, Marchesi L, Manzo G, Giovannini C. [Behavior of basal values and circadian rhythm of ACTH, cortisol, PRL and GH in a high-protein diet]. Boll Soc Ital Biol Sper. 1981 May 15;57(9):963-9. Italian.
- Suminski RR, Robertson RJ, Goss FL, Arslanian S, Kang J, DaSilva S, Utter AC, Metz KF. Acute effect of amino acid ingestion and resistance exercise on plasma growth hormone concentration in young men. Int J Sport Nutr. 1997 Mar;7(1):48-60.
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