KETOgenic Diet Therapy in Patients With ACROmegaly (KETOACRO)

Ketogenic Diet Therapy in Patients With Acromegaly

Acromegaly is caused by a tumour located at the base of the brain in the pituitary gland that produces too much growth hormone (GH). Symptoms caused by the excess of GH, and consequently increased insulin like growth factor 1 (IGF-1), are disproportionate growth of body parts, fluid retention, snoring and excessive perspiration. The various metabolic changes that occur due to acromegaly increase the risk for insulin resistance, diabetes mellitus, arterial hypertension, sleep apnoea and thus an increased risk of cardiovascular disease if left untreated. The result is signs and symptoms, increased mortality, morbidity, and greatly reduced quality of life (QoL). Normalisation of GH and IGF-1 gives a normalisation of mortality, however morbidity and QoL do not (completely) normalise. After surgery, a somatostatin analogue is the primary medical treatment, however, normalisation occurs in only 40% of patients.

Recently, in a proof-of-principle study, the researchers showed that a 2-week ketogenic diet (low in carbohydrates) in patients with somatostatin analogues could significantly reduce IGF-1 values. Patients felt better and sometimes even needed less somatostatin analogues. This proof of concept led to the new hypothesis that acromegaly patients with somatostatin analogues should possibly be treated with a eucaloric low-carbohydrate ketogenic diet for a longer period of time to improve their biochemistry, symptoms and QoL. Additionally, this diet can make a significant contribution in the treatment of insulin resistance and glucose intolerance that often occur in this patient group.

Study Overview

• Status: Recruiting
• Conditions: Acromegaly Due to Pituitary Adenoma; Mediterranean Diet; Ketogenic Diet
• Intervention / Treatment: Dietary supplement: Ketogenic diet; Dietary supplement: Mediterranean diet

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Kirsten A. Berk, Dr.; Phone Number: +31 0107033055; Email: k.berk@erasmusmc.nl
• Study Contact Backup: Name: Eline te Nijenhuis-Noort, MSc; Phone Number: +31 0107033055; Email: l.tenijenhuis-noort@erasmusmc.nl

Study Locations

• Netherlands
  • Rotterdam, Netherlands, 3015 GE
    • Recruiting
    • Erasmus Medical Center
    • Contact: Eline te Nijenhuis-Noort, MSc; Phone Number: +31-0107033055; Email: l.tenijenhuis-noort@erasmusmc.nl
    • Contact: Kirsten A. Berk, Dr.; Phone Number: +31-0107033055; Email: k.berk@erasmusmc.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female, 18 years or older
• Diagnosis of acromegaly based on elevated GH and/or IGF-I levels due to a pituitary tumor
• IGF-I levels above 80% upper limit of the normal range (xULN)) on a stable medication dose for at least 4 months
• Written informed consent

Exclusion Criteria:

• Pregnancy or breastfeeding
• Pegvisomant treatment
• Has undergone pituitary surgery or radiotherapy within 6 months prior to s study entry;
• It is anticipated that the patient will receive pituitary surgery or radiotherapy during the study;
• History or presence of epilepsy;
• Participation in a trail of an experimental drug or device within 30 days prior to screening;
• Has a mental condition rendering the subject unable to understand the nature, scope and possible consequences of the study
• Screening HbA1c > 6,5%;
• Use of antidiabetic medication other than Metformin

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: People with acromegaly following Ketogenic diet; A eucaloric ketogenic diet (30-40 g carbohydrate per day) for 3 months, followed by a less strict ketogenic diet (50-60 g carbohydrate per day) for another 3 months.	Dietary supplement: Ketogenic diet; A eucaloric ketogenic diet (30-40 g carbohydrate per day) for 3 months, followed by a less strict ketogenic diet (50-60 g carbohydrate per day) for another 3 months.
Active Comparator: People with acromegaly following Mediterranean diet; The control group will receive a eucaloric diet according to the national healthy food guidelines/Mediterranean diet.	Dietary supplement: Mediterranean diet; The control group will receive a eucaloric diet according to the national healthy food guidelines/Mediterranean diet.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
IGF-1	Difference in IGF-1 (expressed as times the upper limit of the normal range (xULN) in nmol/L) between control and intervention group.	At baseline, 3 months and 6 months.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Food intake	Food intake (3-day food diary, via 'Eetmeter Voedingscentrum') in kcal, grams of carbohydrates, proteins, saturated fat and total fat, fibers and full-fledged diet (yes/no).	At baseline, 3 months and 6 months.
Quality of Life questionnaire	Quality of Life questionnaire AcroQol (Acromegaly Quality of Life questionnaire); a 5 point likertscale assessing frequency of occurrence (always [1] to never [5]) or degree of agreement (completely agree [1] to completely disagree [5]) with the statements), which assesses physical and psychological aspects of quality of life in 22 questions.	At baseline, 3 months and 6 months.
Quality of Life questionnaire	PASQ= QoL about symptoms (Patient-Assessed Acromegaly Symptom Questionnaire) and consists of 5 acromegaly-related symptoms (soft-tissue swelling, arthralgia, headache, excessive perspiration, and fatigue), which are measured on a scale of 0 to 8 points (a higher score indicating more severe symptoms), and a cumulative score (scale 0 to 40 points) can be calculated by adding the individual components )).	At baseline, 3 months and 6 months.
Qualtity of Life questionnaire	D-KETOcheck questionnaire; consist of 11 questions of the ketogenic which are measured on a scale of 0-4 points (a higher score indicating stronger agreement to the ketogenic diet) for patients in arm of Ketogenic diet.	At baseline, 3 months and 6 months.
Serum parameters	GH level in ug/l	At baseline, 3 months and 6 months.
Serum parameters	IGF1 level in nmol/l	At baseline, 3 months and 6 months.
Serum Parameters	Fasting plasma glucose in mmol/l	At baseline, 3 months and 6 months.
Serum parameters	Fasting insulin in pmol/l	At baseline, 3 months and 6 months.
Serum parameters	HbA1c in mmol/mol	At baseline, 3 months and 6 months.
Serum parameters	Total cholesterol in mmol/l	At baseline, 3 months and 6 months.
Serum parameters	HDL-cholesterol in mmol/l	At baseline, 3 months and 6 months.
Serum parameters	LDL-cholesterol in mmol/l	At baseline, 3 months and 6 months.
Serum parameters	Triglycerides in mmol/l	At baseline, 3 months and 6 months.
Serum parameters	Free fatty acids in mmol/l	At baseline, 3 months and 6 months.
Serum parameters	β-Hydroxybutyrate in mmol/l	At baseline, 3 months and 6 months.
Anthropometry	Height in m	At baseline, 3 months and 6 months.
Anthropometry	Weigth in kg	At baseline, 3 months and 6 months.
Anthropometry	BMI in kg/m2	At baseline, 3 months and 6 months.
Anthropometry	Fat mass in kg and in percent	At baseline, 3 months and 6 months.
Anthropometry	Fat free mass (skeletal muscle mass) in kg	At baseline, 3 months and 6 months.
Anthropometry	Body water in percent	At baseline, 3 months and 6 months.
Anthropometry	Hand grip strength in kg	At baseline, 3 months and 6 months.
Anthropometry	Resting energy expenditure in kcal/day.	At baseline, 3 months and 6 months.

Collaborators and Investigators

• Sponsor: Erasmus Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2023
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): May 1, 2028

Study Registration Dates

• First Submitted: March 6, 2025
• First Submitted That Met QC Criteria: April 25, 2025
• First Posted (Actual): April 29, 2025

Study Record Updates

• Last Update Posted (Actual): April 29, 2025
• Last Update Submitted That Met QC Criteria: April 25, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Bone Diseases; Musculoskeletal Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Endocrine Gland Neoplasms; Neoplasms, Glandular and Epithelial; Nervous System Neoplasms; Central Nervous System Neoplasms; Hypothalamic Diseases; Hypothalamic Neoplasms; Supratentorial Neoplasms; Brain Neoplasms; Hyperpituitarism; Pituitary Diseases; Bone Diseases, Endocrine; Adenoma; Pituitary Neoplasms; Acromegaly; Growth Hormone-Secreting Pituitary Adenoma
• Other Study ID Numbers: NL8384107823

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No