Acromegaly Due to Pituitary AdenomaPasiAcroKetoNCT07866846
Managing Pasireotide-associated Hyperglycaemia in Acromegaly With Ketogenic Diet
A study testing Ketogenic diet and Diabetes Medication in people with Acromegaly Due to Pituitary Adenoma and Hyperglycemia, run by Leiden University Medical Center at 1 site in Netherlands.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acromegaly Due to Pituitary Adenoma, Hyperglycemia, Ketogenic Diet
- What is being tested?
- Ketogenic diet and Diabetes Medication
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteNetherlands
- Study dates
- 29 Jul 2025to 30 Apr 2028
- Phase
- Interventional
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- All patients with acromegaly eligible for inclusion are patients in whom pasireotide is considered in the clinical setting.
- Adult patients with a confirmed diagnosis of acromegaly (for whom surgery is not an option, or for whom surgery has failed) and with either 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%).
- Adult patients with a confirmed diagnosis of acromegaly (for whom surgery is not an option, or for whom surgery has failed) and with either 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%) and ≤64 mmol/L (8.0%) which can first be treated and stabilized with metformine prior to rescreening and baseline measurement and are eligible if they achieve a Hba1c <44 mmol/L (6.2%).
- 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.
- Age ≥18 years
- 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)
Who cannot join
- Has undergone pituitary surgery within 6 months prior to study entry;
- Has undergone radiotherapy within 2 years prior to study entry;
- Patients using pasireotide at screening.
- Patients who have a contraindication to metformin, sitagliptin, liraglutide, or insulin.
- Diabetes mellitus type 2 patients receiving diabetic medication other than metformin or with poor glycaemic control, defined as HbA1c ≥9.0% (less stringent cut-off) at screening.
- Diabetes mellitus type 1.
- Life-threatening diabetic ketoacidosis or diabetic hyperosmolar coma.
- It is anticipated that the patient receives pituitary surgery or radiotherapy during the study.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Netherlands1 site, 1 recruiting
- Recruiting
Leiden University Medical Centre
Leiden, South Holland, 2300 RC
Eline te Nijenhuis-Noort, MSc, PhD student, +31637444875, l.c.te_nijenhuis@lumc.nl
Nienke R. Biermasz, Prof. dr.
About this study
Official title: 'Managing Pasireotide-associated Hyperglycaemia in Acromegaly With Eucaloric Very-low Carbohydrate Ketogenic Diet Versus Diabetes Medication: a Multicentre, Randomized, Open-label Proof-of-concept Study'
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:
Read more
- Differences between eucaloric very-low carbohydrate ketogenic diet and standard of care (diabetes medication) regarding:
- Proportion of patients with target HbA1c (<48mmol/L / <6.5%) achieved without glucose lowering drugs (beyond metformine monotherapy) in both arms
- Evaluation and sustainability of glycaemic control (HbA1c) and (dosage of) anti-diabetic drugs need to reach control
- Biochemical control, and symptom score of acromegaly
- Quality of life
- Proportion of patients on 40 and 60 mg, proportion with normal IGF-1, tolerability, and safety of pasireotide
- Exploratory evaluation of all eligible subjects considered for and started with pasireotide treatment to get a better insight into these complicated acromegaly patients and their metabolic profile.
- Exploratory evaluation of other timepoints (start of pasireotide) to analyse course of Hba1c development from start of pasireotide until the end of the core study Study design: Study type: multicenter combined observational and interventional randomized controlled study. Allocation: randomized (1:1 ratio). Intervention model: parallel assignment. Masking: non (open-label). Primary purpose: supportive care.
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.
- Being tested
- Ketogenic diet, Diabetes Medication
- Medical subject headings
- Growth Hormone-Secreting Pituitary Adenoma, Hyperglycemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ketogenic dietDietary supplement
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.
Diabetes MedicationDrug
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%).
| Study group | Role | What they receive |
|---|---|---|
| Ketogenic diet | Experimental | 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. Receives: Dietary Supplement: Ketogenic diet |
| Antidiabetic drugs, standard care | Active comparator | 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. Receives: Drug: Diabetes Medication |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: At baseline, and 3 months, 7 months, 9, 11 and 13 months after initiation of pasireotide treatment.
Secondary outcomes (23)
Dietary intake of energy
Dietary intake assessed using a 3 days food diary. Total energy intake (kcal/day) will be quantified.
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline
Body weight
Body weight, expressed in kilograms (kg), measured as part of the anthropometric assessment.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline, 9 and 13 months after initiation of the intervention.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Oct 2026
- Study start29 Jul 2025
- Primary completion31 Dec 2027 (estimated)
- Study completion30 Apr 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acromegaly Due to Pituitary AdenomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Leiden University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, nrbiermasz, Leiden University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07866846
- Sponsor's protocol ID
- NL86430.058.24
- Acronym
- PasiAcroKeto
- Status last verified
- Oct 2026
- First submitted
- 27 Jul 2026
- Last updated
- 8 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes