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CompletedNCT07100587Updated Sep 5, 2025

Ketogenic vs. Mediterranean Diet on Metabolic and Hormonal Parameters in Patients With Active Acromegaly

An interventional study of Ketogenic diet and Mediterranean diet in Acromegaly, sponsored by University of Palermo. Completed at 1 site in Italy. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-09-05.

Sponsored by University of Palermo · Not applicable, Interventional, and Treatment

Phase
Not applicable
Study type
Interventional
Enrollment
26
Allocation
Non-randomized
Ages
18 Years and older
Sex
All
01

Study summary

This prospective, single-center, crossover study aims to evaluate the metabolic and hormonal effects of a ketogenic diet compared to a Mediterranean diet in patients with active acromegaly. Twenty-six adult patients with biochemically confirmed active acromegaly will undergo a three-week ketogenic diet followed by a three-week Mediterranean diet, with a two-week transitional phase. The primary outcome is the change in serum IGF-1 levels. Secondary outcomes include changes in anthropometric, biochemical, and inflammatory parameters. The study also explores the feasibility and safety of a structured ketogenic dietary intervention in this population.

Read the detailed description

Acromegaly is a rare endocrine disorder characterized by excessive secretion of growth hormone (GH) and insulin-like growth factor 1 (IGF-1), often leading to metabolic complications including insulin resistance, diabetes mellitus, and hepatic steatosis. Nutritional status is a key regulator of the somatotropic axis, and recent evidence suggests that specific dietary patterns can modulate GH and IGF-1 secretion. The ketogenic diet (KD), characterized by high fat, moderate protein, and very low carbohydrate intake, induces nutritional ketosis, improves insulin sensitivity, and reduces circulating insulin levels. These effects may influence the hepatic expression of GH receptors and IGF-1 production. Preliminary data suggest that KD may reduce IGF-1 levels in patients with acromegaly.

This study is designed as a single-arm crossover trial involving 26 patients with active acromegaly. All participants will follow a structured ketogenic diet for three weeks (\~1200 kcal/day, carbohydrates \<30 g/day), followed by a two-week transition phase, and then a Mediterranean diet for three weeks (\~1200 kcal/day, plant-based, rich in olive oil and fish). Baseline, post-KD, and post-Mediterranean assessments will include serum IGF-1 and GH levels, anthropometric measurements, body composition (via bioelectrical impedance analysis), liver enzymes, lipid profile, insulin resistance indices (HOMA-IR), and inflammatory markers (c-reactive protein, neutrophil to lymphocyte ratio, platelet to lymphocyte ratio).

The primary endpoint is the within-subject change in serum IGF-1 concentration. Secondary endpoints include changes in metabolic and inflammatory markers. Antidiabetic medications will be temporarily discontinued during the ketogenic phase under clinical supervision in patients not requiring insulin. The study is expected to provide novel insights into the impact of dietary modulation on the somatotropic axis in acromegaly and may inform future integrative therapeutic strategies.

02

Conditions studied

  • Acromegaly

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Keywords

  • ketogenic diet
  • mediterranean diet
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Age ≥ 18 years
  • Confirmed diagnosis of active acromegaly (elevated IGF-1, GH non-suppressible at OGTT)
  • Stable medical therapy for ≥ 3 months
  • BMI 25-40 kg/m²
  • Informed consent signed

Exclusion criteria

Exclusion Criteria:

  • Type 1 diabetes or insulin-treated type 2 diabetes mellitus
  • History of ketoacidosis
  • Active malignancy, decompensated liver/kidney disease
  • Severe psychiatric disorders or eating disorders
  • Pregnancy or breastfeeding
04

Study design

Phase
Not applicable
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Crossover assignment
Masking
Single (Outcomes assessor)
Enrollment
26 participants (actual)

Study arms

  • Experimental
    Arm A - Ketogenic Diet (3 weeks)

    Participants will follow a structured ketogenic diet for 3 weeks (\~1200 kcal/day, \<30 g/day carbohydrates) to induce nutritional ketosis.

    Behavioral: Ketogenic diet

  • Active comparator
    Arm B: Mediterranean Diet

    Following a 2-week transition phase, participants will switch to a Mediterranean diet for 3 weeks (\~1200 kcal/day), rich in olive oil, vegetables, whole grains, and moderate protein intake.

    Behavioral: Mediterranean diet

Interventions

  • BehavioralKetogenic diet

    A structured, equicaloric ketogenic diet providing approximately 1200 kcal/day, consisting of high fat (70-80 g/day), moderate protein (80-90 g/day), and very low carbohydrate intake (20-30 g/day), primarily from non-starchy vegetables. The diet is administered for 3 consecutive weeks to induce nutritional ketosis. A sugar-free multivitamin supplement is provided throughout the intervention.

  • BehavioralMediterranean diet

    A structured Mediterranean diet administered for 3 weeks following a 2-week transition phase. The diet provides approximately 1200 kcal/day and emphasizes plant-based foods, extra virgin olive oil as the main fat source, moderate consumption of fish, dairy products, and whole grains, with limited red meat and processed foods.

05

What researchers measure

Primary outcomes

  1. Disease control

    Change in serum IGF-1 levels after ketogenic and Mediterranean diets (paired comparison)

    Time frame: 3 weeks

Secondary outcomes

  1. Metabolic outcomes

    Change in fasting glucose (mg/dL)

    Time frame: 3 weeks

  2. Metabolic outcomes

    Change in fasting insulin (µU/mL)

    Time frame: 3 weeks

  3. Metabolic outcomes

    Change in HOMA-IR (unitless)

    Time frame: 3 weeks

  4. Anthropometric outcomes

    Change in body weight (kg)

    Time frame: 3 weeks

  5. Anthropometric outcomes

    Change in Body Mass Index (BMI) (kg/m²)

    Time frame: 3 weeks

  6. Anthropometric outcomes

    Change in waist circumference (cm)

    Time frame: 3 weeks

  7. Liver outcomes

    Change in transaminases (U/L)

    Time frame: 3 weeks

  8. Lean and fat masses

    Change in lean and fat mass (only after ketogenic diet)

    Time frame: 3 weeks

06

Study locations

1 site
  • Policlinico Paolo Giaccone
    Palermo, Italy
07

References and documents

Individual participant data

Plan to share: No — Individual participant data (IPD) will not be shared. This decision is based on institutional policy and ethical considerations, as the study involves a relatively small and identifiable patient population with a rare endocrine disorder. Data sharing may compromise patient confidentiality despite de-identification procedures.

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT07100587
Lead sponsor
University of Palermo
Responsible party
Valentina Guarnotta (Professor, University of Palermo) — Principal investigator
First posted
Aug 3, 2025
Start date
Jun 30, 2024
Primary completion
May 31, 2025
Completion
Jul 2, 2025
Last update
Sep 5, 2025

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
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