[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100659525":3},{"organization":4,"outcomesModule":7,"designInfo":119,"detailedDescription":122,"studyPopulation":122,"armGroups":126,"interventions":139,"overallOfficials":122,"centralContacts":149,"locations":159,"responsibleParty":184,"collaborators":122,"id":187,"slug":188,"hasResults":189,"nctId":190,"briefTitle":191,"officialTitle":192,"acronym":193,"eligibilityCriteria":194,"healthyVolunteers":189,"sex":195,"minAge":196,"maxAge":122,"enrollmentInfo":197,"targetDuration":122,"studyType":200,"phases":201,"briefSummary":203,"conditions":204,"keywords":122,"overallStatus":162,"whyStopped":122,"lastUpdateSubmitDate":209,"lastUpdatePostDateStruct":210,"startDateStruct":213,"completionDateStruct":215,"leadSponsor":217,"locationsCount":218},{"fullName":5,"class":6},"Leiden University Medical Center","OTHER",{"primaryOutcomes":8,"secondaryOutcomes":13,"otherOutcomes":91},[9],{"measure":10,"description":11,"timeFrame":12},"Hemoglobin A1c (HbA1c) level","Glycaemic control will be assessed by measurement of HbA1c, expressed in mmol\u002Fmol. The outcome measure is the HbA1c value at each scheduled study assessment.","At baseline, and 3 months, 7 months, 9, 11 and 13 months after initiation of pasireotide treatment.",[14,18,21,24,27,30,33,37,41,45,49,53,56,59,62,65,68,71,75,78,82,85,88],{"measure":15,"description":16,"timeFrame":17},"Dietary intake of energy","Dietary intake assessed using a 3 days food diary. Total energy intake (kcal\u002Fday) will be quantified.","Baseline and at 3, 7, 9 and 13 month after initiation of pasireotide treatment.",{"measure":19,"description":20,"timeFrame":17},"Dietary intake of carbohydrates","Dietary intake assessed using a 3-day food diary. Carbohydrate intake will be quantified as absolute intake (g\u002Fday) and as a percentage of total energy intake (%E).",{"measure":22,"description":23,"timeFrame":17},"Dietary intake of proteins","Dietary intake assessed using a 3-day food diary. Protein intake will be quantified as absolute intake (g\u002Fday) and as a percentage of total energy intake (%E).",{"measure":25,"description":26,"timeFrame":17},"Dietary intake of fat","Dietary intake assessed using a 3-day food diary. Fat intake will be quantified as absolute intake (g\u002Fday) and as a percentage of total energy intake (%E).",{"measure":28,"description":29,"timeFrame":17},"Dietary intake of fiber","Dietary intake assessed using a 3-day food diary. Fiber intake will be quantified as absolute intake (g\u002Fday).",{"measure":31,"description":32,"timeFrame":17},"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\u002Fno).",{"measure":34,"description":35,"timeFrame":36},"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.","Baseline, 3 months, 7 months, 11 months and 13 months after start intervention.",{"measure":38,"description":39,"timeFrame":40},"Hand grip strength","Hand grip strength, expressed in kilograms (kg), measured using a hand dynamometer as an indicator of muscle strength and physical function.","Baseline and 3, 7, 9, 11, and 13 months after initiation of the intervention.",{"measure":42,"description":43,"timeFrame":44},"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.","At start intervention, and 3, 7, 11 and 13 months after initiation.",{"measure":46,"description":47,"timeFrame":48},"Height","Standing height, expressed in meters (m), measured as part of the anthropometric assessment.","Baseline",{"measure":50,"description":51,"timeFrame":52},"Body weight","Body weight, expressed in kilograms (kg), measured as part of the anthropometric assessment.","Baseline, 3, 7, 9, 11 and 13 months after initiation of the intervention.",{"measure":54,"description":55,"timeFrame":52},"Body Mass Index","Body mass index (BMI), expressed in kg\u002Fm², calculated as body weight in kilograms divided by the square of height in meters (kg\u002Fm²). BMI is measured as part of the anthropometric assessment.",{"measure":57,"description":58,"timeFrame":40},"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.",{"measure":60,"description":61,"timeFrame":40},"Fat mass","Body fat mass, expressed in kilograms (kg) and as a percentage of total body weight (%), measured as part of the anthropometric assessment.",{"measure":63,"description":64,"timeFrame":40},"Resting energy expenditure","Resting energy expenditure (REE), expressed in kilocalories per day (kcal\u002Fday), measured to assess energy metabolism under resting conditions.",{"measure":66,"description":67,"timeFrame":40},"Insulin-like Growth Factor 1 (IGF-1) level","Plasma insulin-like growth factor 1 (IGF-1) concentration, expressed in nmol\u002FL, measured to assess biochemical disease control.",{"measure":69,"description":70,"timeFrame":40},"Growth hormone (GH) level","Serum growth hormone (GH) concentration, expressed in µg\u002FL, measured as a marker of biochemical control of acromegaly.",{"measure":72,"description":73,"timeFrame":74},"Fasting plasma glucose level","Fasting plasma glucose concentration, expressed in mmol\u002FL, measured after an overnight fast to assess glycaemic control.","Baseline and 3, 7, 9, 11, and 13 months after initiation of the intervention",{"measure":76,"description":77,"timeFrame":40},"Fasting insulin in pmol\u002Fl","Fasting insulin concentration, expressed in pmol\u002FL, measured after an overnight fast to assess insulin secretion and metabolic status.",{"measure":79,"description":80,"timeFrame":81},"Total cholesterol level","Total cholesterol concentration, expressed in mmol\u002FL, measured to assess lipid metabolism and cardiovascular risk.","Baseline, 9 and 13 months after initiation of the intervention.",{"measure":83,"description":84,"timeFrame":81},"High-density lipoprotein (HDL) cholesterol level","High-density lipoprotein (HDL) cholesterol concentration, expressed in mmol\u002FL, measured to assess lipid metabolism and cardiovascular risk profile.",{"measure":86,"description":87,"timeFrame":81},"Low-density lipoprotein (LDL) cholesterol level Show more lines","Low-density lipoprotein (LDL) cholesterol concentration, expressed in mmol\u002FL, measured to assess lipid metabolism and cardiovascular risk profile.",{"measure":89,"description":90,"timeFrame":81},"Triglyceride level","Triglyceride concentration, expressed in mmol\u002FL, measured to assess lipid metabolism and cardiovascular risk profile.",[92,96,99,103,106,109,113,116],{"measure":93,"description":94,"timeFrame":95},"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.","Only for patients randomized to ketogenic diet; at 2 weeks, 8 weeks, 16 weeks and 32 weeks of ketogenic diet.",{"measure":97,"description":98,"timeFrame":40},"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.",{"measure":100,"description":101,"timeFrame":102},"Free fatty acid level","Plasma free fatty acid concentration, expressed in mmol\u002FL, measured as a marker of ketogenesis.","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.",{"measure":104,"description":105,"timeFrame":81},"Beta-hydroxybutyrate level","Plasma beta-hydroxybutyrate concentration, expressed in mmol\u002FL, measured as a marker of ketogenesis.",{"measure":107,"description":108,"timeFrame":40},"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.",{"measure":110,"description":111,"timeFrame":112},"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.","Through study completion, an average of 1 year",{"measure":114,"description":115,"timeFrame":112},"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.",{"measure":117,"description":118,"timeFrame":112},"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.",{"allocation":120,"interventionModel":121,"interventionModelDescription":122,"primaryPurpose":123,"observationalModel":122,"timePerspective":122,"maskingInfo":124},"RANDOMIZED","PARALLEL",null,"TREATMENT",{"masking":125,"maskingDescription":122,"whoMasked":122},"NONE",[127,133],{"label":128,"type":129,"description":130,"interventionNames":131},"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\u002FL) will be randomized 1:1 to ketogenic diet or antidiabetic drug.\n\nAn ad libitum ketogenic diet of which only the amount of carbohydrates is restricted (\\\u003C40 g of carbohydrate, approximately 155 g of fat, and approximately 115 g of protein per day). This amount of carbohydrates will lead to ketogenesis.",[132],"Dietary Supplement: Ketogenic diet",{"label":134,"type":135,"description":136,"interventionNames":137},"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.",[138],"Drug: Diabetes Medication",[140,144],{"type":141,"name":128,"description":142,"armGroupLabels":143,"otherNames":122},"DIETARY_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 (\\\u003C40 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\u002Fday, for men 2500 kcal\u002Fday.",[128],{"type":145,"name":146,"description":147,"armGroupLabels":148,"otherNames":122},"DRUG","Diabetes Medication","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 \\\u003C44 mmol\u002FL (Hba1c\\\u003C6.2%).",[134],[150,155],{"name":151,"role":152,"phone":153,"phoneExt":122,"email":154},"Nienke R. Biermasz, Prof. dr.","CONTACT","(+31)0715263082","n.r.biermasz@lumc.nl",{"name":156,"role":152,"phone":157,"phoneExt":122,"email":158},"Iris C.M. Pelsma,, MSc","(+31)715298943","i.c.m.pelsma@lumc.nl",[160],{"facility":161,"status":162,"city":163,"state":164,"zip":165,"country":166,"countryCode":167,"cosmosGeoPoint":168,"geoPoint":173,"contacts":174},"Leiden University Medical Centre","RECRUITING","Leiden","South Holland","2300 RC","Netherlands","NL",{"type":169,"coordinates":170},"Point",[171,172],4.49306,52.15833,{"lat":172,"lon":171},[175,179,181],{"name":176,"role":152,"phone":177,"phoneExt":122,"email":178},"Eline te Nijenhuis-Noort, MSc, PhD student","+31637444875","l.c.te_nijenhuis@lumc.nl",{"name":151,"role":180,"phone":122,"phoneExt":122,"email":122},"PRINCIPAL_INVESTIGATOR",{"name":182,"role":183,"phone":122,"phoneExt":122,"email":122},"Iris C.M. Pelsma, MSc","SUB_INVESTIGATOR",{"type":180,"investigatorFullName":185,"investigatorTitle":186,"investigatorAffiliation":5,"oldNameTitle":122,"oldOrganization":122},"nrbiermasz","Principal Investigator","100659525","managing-pasireotide-associated-hyperglycaemia-in-acromegaly-with-ketogenic-diet-100659525",false,"NCT07866846","Managing Pasireotide-associated Hyperglycaemia in Acromegaly With Ketogenic Diet","'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'","PasiAcroKeto","Inclusion Criteria:\n\nAll patients with acromegaly eligible for inclusion are patients in whom pasireotide is considered in the clinical setting.\n\n* 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\u002For IGF-1 control (\\>0.8xULN) or active disease symptoms with first-generation SRL, or with inadequately GH and\u002For 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 \\\u003C44 mmol\u002FL (6.2%).\n* 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\u002For IGF-1 control (\\>0.8xULN) or active disease symptoms with first-generation SRL, or with inadequately GH and\u002For 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\u002FL (6.2%) and ≤64 mmol\u002FL (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 \\\u003C44 mmol\u002FL (6.2%).\n\nBecause 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.\n\n* Age ≥18 years\n* Confirmed diagnosis of acromegaly (for whom surgery is not an option, or for whom surgery has failed) and with inadequately GH and\u002For IGF-1 control (\\>0.8xULN)\n\nExclusion Criteria:\n\n* Has undergone pituitary surgery within 6 months prior to study entry;\n* Has undergone radiotherapy within 2 years prior to study entry;\n* Patients using pasireotide at screening.\n* Patients who have a contraindication to metformin, sitagliptin, liraglutide, or insulin.\n* 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.\n* Diabetes mellitus type 1.\n* Life-threatening diabetic ketoacidosis or diabetic hyperosmolar coma.\n* It is anticipated that the patient receives pituitary surgery or radiotherapy during the study.","ALL","18 Years",{"count":198,"type":199},30,"ESTIMATED","INTERVENTIONAL",[202],"NA","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.\n\nObjective: 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:\n\n* Differences between eucaloric very-low carbohydrate ketogenic diet and standard of care (diabetes medication) regarding:\n\n  * Proportion of patients with target HbA1c (\\\u003C48mmol\u002FL \u002F \\\u003C6.5%) achieved without glucose lowering drugs (beyond metformine monotherapy) in both arms\n  * Evaluation and sustainability of glycaemic control (HbA1c) and (dosage of) anti-diabetic drugs need to reach control\n  * Biochemical control, and symptom score of acromegaly\n  * Quality of life\n  * Proportion of patients on 40 and 60 mg, proportion with normal IGF-1, tolerability, and safety of pasireotide\n* 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.\n* 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.\n\nStudy 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\u002For IGF-1 control (\\>0.8xULN) or active disease symptoms with first-generation SRL, or with inadequately GH and\u002For 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 \\\u003C44 mmol\u002FL (6.2%) - including those pre-treated with metformin in case of HbA1c ≥44 mmol\u002FL (6.2%) and ≤64 mmol\u002FL (8.0%) - in whom pasireotide is considered in the clinical setting.\n\nIntervention (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 (\\\u003C40 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).\n\nMain study parameters\u002Fendpoints:\n\nEvaluation of effect of treatment with eucaloric very-low carbohydrate ketogenic diet or diabetes medication on glycaemic control of pasireotide:\n\n\\- 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\u002Fanthropometric 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.",[205,206,207,208],"Acromegaly Due to Pituitary Adenoma","Hyperglycemia","Ketogenic Diet","Standard Care Control","2026-10-05",{"date":211,"type":212},"2026-10-08","ACTUAL",{"date":214,"type":212},"2025-07-29",{"date":216,"type":199},"2028-04-30",{"name":5,"class":6},1]