KETOACRO

Background

Acromegaly is caused by a pituitary gland tumor at the base of the brain that produces excess growth hormone (GH), leading to elevated insulin-like growth factor 1 (IGF-1) and symptoms such as disproportionate body growth, fluid retention, snoring, and excessive sweating. These hormonal and metabolic changes increase the risk of diabetes, hypertension, sleep apnea, and cardiovascular disease, and while surgery followed by somatostatin analogues can normalize GH and IGF-1 in about 40% of patients, morbidity and quality of life often remain impaired despite reduced mortality.

In a proof-of-principle study, we 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.

Objective

To determine the effect of a 6-month eucaloric very-low-carbohydrate ketogenic diet on IGF-I levels in adult acromegaly patients.

Study design

A single-centre randomised controlled trial

Study population

60 patients (≥18 years) with active acromegaly on stable medication dose for at least 4 months, and a small subcohort of ten patients with pegvisomant treatment, as a pilot study, with the same recruitement strategy and the same in- and exclusion criteria.

Intervention

A eucaloric ketogenic diet (30-40 g carbohydrate per day) for 3 months, followed by a low‑carb diet (50-60 g carbohydrate per day) for another 3 months. The control group will receive a eucaloric diet according to the national healthy food guidelines/Mediterranean diet.

Main study parameters/endpoints

Difference in IGF-1 (expressed as times the upper limit of the normal range (xULN)) between control and intervention group during 6 months of dieting (continuous). Secondary endpoints are Quality of Life, change in body weight, body composition, resting energy expenditure and plasma parameters.

If you have suitable participants, please contact Eline te Nijenhuis or one of the principal investigators if you would like to discuss whether your patient is suitable for this study.

Documents
CCMO/onderzoeksportaal – NL-007031
Subject information letter and subject consent form

Participating hospitals
Erasmus Medical Center
Leiden University Medical Center

Contact information
Coördinating researcher
Mrs. Drs. L.C. (Eline) te Nijenhuis-Noort

ErasmusMC, Department of internal Medicine / dietetics
P.O. Box 2040, internal address: Na-420
3000 CA Rotterdam
Email: l.tenijenhuis-noort@erasmusmc.nl

LUMC, Department of endocrinology
P.O. Box 9600, internal address: C7-Q-057
2300 RC Leiden
Email: l.c.te_nijenhuis@lumc.nl

Principal Investigators
Dr. S.J.C.M.M. Neggers, internist-endocrinologist ErasmusMC
Dr. K.A.C. Berk, university lecturer and dietitian Erasmus MC
Prof. Dr. N.R. Biermasz, internist-endocrinologist LUMC
Dr. J. Refardt, internist-endocrinologist ErasmusMC