Standard Care Control

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: * 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.

Background Leukaemia is the most common cancer in children with 800 diagnoses per year in England. To survive, children need strong treatments like chemotherapy and steroids given usually through clinical trials. The current trial used by the NHS is called ALLTogether. Fifty percent of children become obese during treatment due to increased hunger, cravings for junk foods and lack of physical activity. Obesity raises the chance of cancer relapse by 31%, makes treatment side-effects worse and makes it harder to kill off leukaemia cells, which affects how well children do during treatment, as indicated by minimal residual disease, a key predictor of prognosis. Aims and Objectives This study (called BREVARY) aims to see if we can successfully provide personalised diet and physical activity with behaviour support for children and young people with leukaemia who are being treated with the ALLTogether trial. It will help us figure out if we can perform a bigger study, if this programme could reduce obesity and side-effects and improve survival and wellbeing. How it will be done We plan to randomly assign participants to one of three groups; one group will get both a diet and physical activity plan, another will get only a diet plan, and the last group will receive standard care. This will take place in Hospital Infantil Universitario Nino Jesus, Madrid and Bristol Royal Hospital for Children and Southwest England NHS-sites. The diet and exercise plans will be created in partnership with the children and their families and delivered online or during regular hospital visits. The diet will follow healthy eating guidelines, consider personal food preferences (including cultural and religious needs), treatment side-effects and personal finances. Assessments of fitness and strength will be taken to plan personalised activities. During the study, the following data will also be collected: weight, height, body fat, diet, biomarkers, microbiome, muscle strength and wellbeing at three different times. "One to one" interviews will be conducted at the end to obtain feedback on their experiences with BREVARY. This study aims to find out if children and their families/carers are willing to participate in BREVARY, if enough people sign up and stay until the end and if our interventions and health measurements are appropriate. Potential Impact The results will help determine if a larger study can be performed, if changes are needed and what the cost will be. The study will be disseminated through networks, targeting underserved communities, healthcare professionals and affected families using accessible platforms to spread the word.