An interventional study of Ketogenic diet and Diabetes Medication in Acromegaly Due to Pituitary Adenoma, Hyperglycemia and Ketogenic Diet, sponsored by Leiden University Medical Center. Recruiting at 1 site in Netherlands. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-10-08.
Sponsored by Leiden University Medical Center · Not applicable, Interventional, and Treatment
Rationale: Pasireotide is a second line medical treatment for acromegaly that can add value for patients with insufficient control of disease on 1st generation SRL, or 1st generation SRL + pegvisomant. A well-known advserse effect of pasireotide is development of hyperglycemia in 50-70% of cases. Eucaloric very-low carbohydrate ketogenic diet (VLCKD) improves hemoglobin a1c (HbA1c) and fasting plasma glucose (FPG) levels and can show even a long-term effect on glucose regulation in patients with acromegaly. Moreover, the eucaloric VLCKD has improved disease control in patients with acromegaly.
Objective: The primary objective of this study is to evaluate the change in HbA1c from start of intervention (baseline of the core study) to post-four months of ketogenic diet compared to standard of care (core study) in patients developing pasireotide-induced hyperglycemia.The secondary objectives are to evaluate:
Differences between eucaloric very-low carbohydrate ketogenic diet and standard of care (diabetes medication) regarding:
Study population: Adult patients with a confirmed diagnosis of acromegaly (for whom surgery is not an option, or for whom surgery has failed) and with inadequately GH and/or IGF-1 control (>0.8xULN) or active disease symptoms with first-generation SRL, or with inadequately GH and/or IGF-1 control (>0.8xULN) or active disease symptoms on second-line medical treatments for acromegaly (pegvisomant monotherapy or combination therapy with first-generation SRL and pegvisomant or dopamine agonist, respectively) and with a baseline Hba1c \<44 mmol/L (6.2%) - including those pre-treated with metformin in case of HbA1c ≥44 mmol/L (6.2%) and ≤64 mmol/L (8.0%) - in whom pasireotide is considered in the clinical setting.
Intervention (if applicable): We aim to include 30 acromegaly patients with pasireotide-induced hyperglycaemia, to ensure that 20 patients complete the 4-month intervention. Subjects will be randomized 1:1 to open-label eucaloric very-low carbohydrate ketogenic diet (\<40 g of carbohydrate) or standard of care (i.e. metformin, followed by sitagliptin (DPP4-inhibitor), incretin-based therapy with liraglutide (GLP-1 receptor agonist), and insulin) at the time hyperglycemia is present. The randomized intervention period is 4 months (core phase of the study). Randomized subjects who reach the end of the randomized phase can continue with the open-label extension, and opt to continue their randomized diet or DM drug treatment or freely choose the other alternative for another 4 months (extension study).
Main study parameters/endpoints:
Evaluation of effect of treatment with eucaloric very-low carbohydrate ketogenic diet or diabetes medication on glycaemic control of pasireotide:
- Change in HbA1c from start core study to the end of the intervention (ketogenic diet vs standard of care) Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Study participants will have 8 visits to the outpatient clinic over a period of 12-15 months. This comes down to 480 minutes in total. During these visits, physical exam/anthropometric measurements will be performed and 2 blood tubes of 2,5 cc will be collected and 3 QoL questionnaires and one food diary will be filled out (total visit: 60 minutes). The usual burden for a single patient is 3-outpatient visits over a period of 1 year, which takes about 60 minutes in total and with the same volume of blood per visit.
699 studies on the registry are indexed under Hyperglycemia; 105 are open to participants now.
This study's planned enrollment of 30 is below the median of 46 across 521 interventional studies indexed under Hyperglycemia.
Browse Hyperglycemia studies →Leiden University Medical Center is the lead sponsor of 327 studies on the registry; 107 are open to participants now.
Counted across the registry records on this site, refreshed daily.
All patients with acromegaly eligible for inclusion are patients in whom pasireotide is considered in the clinical setting.
Because of the low incidence rate of acromegaly and pasireotide use, we can offer patients that are already on chronic treatment with pasireotide and develop newly onset diabetes the interventions. Moreover, as mentioned prior, patients excluded from the interventional study at any time can participate in the observational part of the study.
Exclusion Criteria:
After 3 months of pasireotide treatment, there is an evaluation of glycemic status and acromegalic biochemical control. Patients with hyperglycemia (Hba1c\>6.5% or \>48 mmol/L) will be randomized 1:1 to ketogenic diet or antidiabetic drug. An ad libitum ketogenic diet of which only the amount of carbohydrates is restricted (\<40 g of carbohydrate, approximately 155 g of fat, and approximately 115 g of protein per day). This amount of carbohydrates will lead to ketogenesis.
Dietary Supplement: Ketogenic diet
Subjects randomized to the diabetes medication arm will be treated with diabetic drugs according to the current Dutch guidelines, and the recently published consensus statement for the treatment of pasireotide-induced hyperglycemia.
Drug: Diabetes Medication
Subjects randomized to the eucaloric very-low carbohydrate ketogenic diet start with an ad libitum ketogenic diet of which only the amount of carbohydrates is restricted (\<40 g of carbohydrate, approximately 155 g of fat, and approximately 115 g of protein per day). This amount of carbohydrates will lead to ketogenesis. Emphasis is placed on the use of products high in polyunsaturated and monounsaturated fatty acids (diet margarines, oils, fish, nuts), preferably with vegetable and marine sources of protein, in concordance with the national nutritional guidelines and the Mediterranean diet (11). We aim for a eucaloric diet, not restricting energy intake. For women we aim at 2000 kcal/day, for men 2500 kcal/day.
Subjects randomized to the diabetes medication arm will be treated with diabetic drugs according to the current Dutch guidelines, and the recently published consensus stategement for the treatment of pasireotide-induced hyperglycemia (outlined in Fig 2.) (22). Dose escalation or medication switches are made every 2-4 weeks at the discretion of the treating physician aiming at a normal Hba1c of \<44 mmol/L (Hba1c\<6.2%).
Hemoglobin A1c (HbA1c) level
Glycaemic control will be assessed by measurement of HbA1c, expressed in mmol/mol. The outcome measure is the HbA1c value at each scheduled study assessment.
Time frame: At baseline, and 3 months, 7 months, 9, 11 and 13 months after initiation of pasireotide treatment.
Dietary intake of energy
Dietary intake assessed using a 3 days food diary. Total energy intake (kcal/day) will be quantified.
Time frame: Baseline and at 3, 7, 9 and 13 month after initiation of pasireotide treatment.
Dietary intake of carbohydrates
Dietary intake assessed using a 3-day food diary. Carbohydrate intake will be quantified as absolute intake (g/day) and as a percentage of total energy intake (%E).
Time frame: Baseline and at 3, 7, 9 and 13 month after initiation of pasireotide treatment.
Dietary intake of proteins
Dietary intake assessed using a 3-day food diary. Protein intake will be quantified as absolute intake (g/day) and as a percentage of total energy intake (%E).
Time frame: Baseline and at 3, 7, 9 and 13 month after initiation of pasireotide treatment.
Dietary intake of fat
Dietary intake assessed using a 3-day food diary. Fat intake will be quantified as absolute intake (g/day) and as a percentage of total energy intake (%E).
Time frame: Baseline and at 3, 7, 9 and 13 month after initiation of pasireotide treatment.
Dietary intake of fiber
Dietary intake assessed using a 3-day food diary. Fiber intake will be quantified as absolute intake (g/day).
Time frame: Baseline and at 3, 7, 9 and 13 month after initiation of pasireotide treatment.
Nutritional adequacy of the dietary pattern
Dietary intake will be assessed using a 3-day food diary. Micro-nutrient intake will be quantified and compared with the Recommended Dietary Allowance (RDA) for micro-nutrients. Based on this comparison, the patient's dietary pattern will be classified as nutritionally adequate (yes/no).
Time frame: Baseline and at 3, 7, 9 and 13 month after initiation of pasireotide treatment.
Acromegaly Quality of Life Questionnaire (AcroQoL) score
Quality of life will be assessed using the Acromegaly Quality of Life Questionnaire (AcroQoL), a disease-specific questionnaire consisting of 22 items evaluating physical and psychological aspects of quality of life. Responses are recorded on a 5-point Likert scale assessing frequency of occurrence (1 = always to 5 = never) or degree of agreement (1 = completely agree to 5 = completely disagree). The total AcroQoL score will be used as the outcome measure.
Time frame: Baseline, 3 months, 7 months, 11 months and 13 months after start intervention.
Hand grip strength
Hand grip strength, expressed in kilograms (kg), measured using a hand dynamometer as an indicator of muscle strength and physical function.
Time frame: Baseline and 3, 7, 9, 11, and 13 months after initiation of the intervention.
Change in Patient-Assessed Acromegaly Symptom Questionnaire (PASQ) total score from baseline
Change from baseline in acromegaly symptom burden assessed using the Patient-Assessed Acromegaly Symptom Questionnaire (PASQ). The PASQ evaluates five acromegaly-related symptoms (soft-tissue swelling, arthralgia, headache, excessive perspiration, and fatigue). Each symptom is scored from 0 to 8, with higher scores indicating greater symptom severity. The total PASQ score ranges from 0 to 40.
Time frame: At start intervention, and 3, 7, 11 and 13 months after initiation.
Height
Standing height, expressed in meters (m), measured as part of the anthropometric assessment.
Time frame: Baseline
Body weight
Body weight, expressed in kilograms (kg), measured as part of the anthropometric assessment.
Time frame: Baseline, 3, 7, 9, 11 and 13 months after initiation of the intervention.
Body Mass Index
Body mass index (BMI), expressed in kg/m², calculated as body weight in kilograms divided by the square of height in meters (kg/m²). BMI is measured as part of the anthropometric assessment.
Time frame: Baseline, 3, 7, 9, 11 and 13 months after initiation of the intervention.
Fat-free mass
Fat-free mass, including skeletal muscle mass, expressed in kilograms (kg), measured as part of the anthropometric assessment of the body composition.
Time frame: Baseline and 3, 7, 9, 11, and 13 months after initiation of the intervention.
Fat mass
Body fat mass, expressed in kilograms (kg) and as a percentage of total body weight (%), measured as part of the anthropometric assessment.
Time frame: Baseline and 3, 7, 9, 11, and 13 months after initiation of the intervention.
Resting energy expenditure
Resting energy expenditure (REE), expressed in kilocalories per day (kcal/day), measured to assess energy metabolism under resting conditions.
Time frame: Baseline and 3, 7, 9, 11, and 13 months after initiation of the intervention.
Insulin-like Growth Factor 1 (IGF-1) level
Plasma insulin-like growth factor 1 (IGF-1) concentration, expressed in nmol/L, measured to assess biochemical disease control.
Time frame: Baseline and 3, 7, 9, 11, and 13 months after initiation of the intervention.
Growth hormone (GH) level
Serum growth hormone (GH) concentration, expressed in µg/L, measured as a marker of biochemical control of acromegaly.
Time frame: Baseline and 3, 7, 9, 11, and 13 months after initiation of the intervention.
Fasting plasma glucose level
Fasting plasma glucose concentration, expressed in mmol/L, measured after an overnight fast to assess glycaemic control.
Time frame: Baseline and 3, 7, 9, 11, and 13 months after initiation of the intervention
Fasting insulin in pmol/l
Fasting insulin concentration, expressed in pmol/L, measured after an overnight fast to assess insulin secretion and metabolic status.
Time frame: Baseline and 3, 7, 9, 11, and 13 months after initiation of the intervention.
Total cholesterol level
Total cholesterol concentration, expressed in mmol/L, measured to assess lipid metabolism and cardiovascular risk.
Time frame: Baseline, 9 and 13 months after initiation of the intervention.
High-density lipoprotein (HDL) cholesterol level
High-density lipoprotein (HDL) cholesterol concentration, expressed in mmol/L, measured to assess lipid metabolism and cardiovascular risk profile.
Time frame: Baseline, 9 and 13 months after initiation of the intervention.
Low-density lipoprotein (LDL) cholesterol level Show more lines
Low-density lipoprotein (LDL) cholesterol concentration, expressed in mmol/L, measured to assess lipid metabolism and cardiovascular risk profile.
Time frame: Baseline, 9 and 13 months after initiation of the intervention.
Triglyceride level
Triglyceride concentration, expressed in mmol/L, measured to assess lipid metabolism and cardiovascular risk profile.
Time frame: Baseline, 9 and 13 months after initiation of the intervention.
D-KETOcheck questionnaire score
Adherence to the ketogenic diet will be assessed using the D-KETOcheck questionnaire in participants assigned to the ketogenic diet intervention. The questionnaire consists of 11 items evaluating adherence to and experiences with the ketogenic diet. Each item is scored on a 5-point scale from 0 to 4, with higher scores indicating stronger agreement with and adherence to the ketogenic diet. The total D-KETOcheck score will be used as the outcome measure.
Time frame: Only for patients randomized to ketogenic diet; at 2 weeks, 8 weeks, 16 weeks and 32 weeks of ketogenic diet.
Phase angle
Phase angle, expressed in degrees (°), measured as part of the anthropometric assessment using bioelectrical impedance analysis (BIA). Phase angle is considered an indicator of cellular health, cell membrane integrity, and nutritional status.
Time frame: Baseline and 3, 7, 9, 11, and 13 months after initiation of the intervention.
Free fatty acid level
Plasma free fatty acid concentration, expressed in mmol/L, measured as a marker of ketogenesis.
Time frame: Samples will be collected at baseline, 9 and 13 months after start of the intervention, and stored for batched analysis at a later time point.
Beta-hydroxybutyrate level
Plasma beta-hydroxybutyrate concentration, expressed in mmol/L, measured as a marker of ketogenesis.
Time frame: Baseline, 9 and 13 months after initiation of the intervention.
Total body water percentage
Total body water, expressed as a percentage of body weight (%), measured as part of the anthropometric assessment to evaluate changes in body fluid status and potential fluid retention (edema), which may influence fat-free mass measurements.
Time frame: Baseline and 3, 7, 9, 11, and 13 months after initiation of the intervention.
Proportion of participants receiving 40 mg or 60 mg pasireotide
Proportion of participants treated with a monthly pasireotide dose of 40 mg or 60 mg during the study period. Dose adjustments are performed according to clinical practice and biochemical disease control of acromegaly.
Time frame: Through study completion, an average of 1 year
Proportion of participants with normalized insulin-like growth factor 1 (IGF-1) levels
Proportion of participants with age- and sex-adjusted normal insulin-like growth factor 1 (IGF-1) levels, assessed as a marker of biochemical control of acromegaly.
Time frame: Through study completion, an average of 1 year
Proportion of participants discontinuing pasireotide due to adverse events
Proportion of participants who permanently discontinue pasireotide treatment due to treatment-related adverse events or intolerance.
Time frame: Through study completion, an average of 1 year
Plan to share: Yes
No publications or documents are linked to this record.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.
Contact study teamGet an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Growth Hormone-Secreting Pituitary Adenoma
Leiden University Medical Center