| Outcome Measures: |
Primary: Change from baseline to the end of treatment in mean glycosylated haemoglobin A1c (HbA1c) level., At baseline and at the end of treatment, a fasting blood sample is taken for measurement of HbA1c levels. Values are calculated as a percentage of total haemoglobin. A decrease from baseline to the end of treatment in base per cent values, a negative value, indicates an improvement., Baseline (Day 1) and End of treatment (Day 85) | Secondary: Change from baseline to the end of treatment in mean fasting plasma glucose concentration., At baseline and at the end of treatment, a fasting blood sample is taken for measurement of fasting plasma glucose concentrations. A decrease from baseline to the end of treatment, a negative value, indicates an improvement., Baseline (Day 1) and End of treatment (Day 85)|Change from baseline to the end of treatment in mean serum glucose concentration two hours post glucose challenge (Oral Glucose Tolerance Test [OGTT]), Fasting blood samples are taken at 0 minutes prior to a glucose drink and at 30 and 120 minutes post drink. The OGTT measures the serum glucose levels at two hours (120 minutes) compared to 0 minutes. The extent of the elevation in serum glucose levels following a glucose drink are compared between baseline and the end of treatment. A reduction in the elevation of serum glucose levels at the end of treatment, a negative value, indicates an improvement., Baseline (Day 1) and End of treatment (Day 85)|Change from baseline to the end of treatment in mean serum fructosamine concentration., At baseline and at the end of treatment, a fasting blood sample is taken for measurement of serum fructosamine concentrations. A decrease from baseline to the end of treatment, a negative value, indicates an improvement., Baseline (Day 1) and End of treatment (Day 85)|Change from baseline to the end of treatment in the number of participants with a HbA1c level below 7%., At baseline and at the end of treatment, a fasting blood sample is taken for measurement of glycosylated haemoglobin A1c levels. Values are calculated as a percentage of total haemoglobin. An increase in the number of participants with HbA1c levels below 7% from baseline to the end of treatment, a positive value, indicates an improvement., Baseline (Day 1) and End of treatment (Day 85)|Change from baseline to the end of treatment in mean fasting plasma insulin concentration., At baseline and at the end of treatment, a fasting blood sample is taken for measurement of fasting plasma insulin concentrations. An increase from baseline to the end of treatment, a positive value, indicates an improvement., Baseline (Day 1) and End of treatment (Day 85)|Change from baseline to the end of treatment in mean insulin resistance measured by Homeostasis Model Assessment 2 (HOMA2-IR)., At baseline and at the end of treatment, a fasting blood sample is taken for measurement of insulin resistance calculated by HOMA2-IR. HOMA2-IR is a computer model that uses fasting plasma insulin and glucose concentrations to estimate insulin resistance, which is the reciprocal of insulin sensitivity (%S) (100/%S) as a percentage of a normal reference population (normal young adults). A decrease from baseline to the end of treatment, a negative value, indicates an improvement., Baseline (Day 1) and End of treatment (Day 85)|Change from baseline to the end of treatment in mean serum insulin concentration two hours post glucose challenge (Oral Glucose Tolerance Test [OGTT]), Fasting blood samples are taken at 0 minutes prior to a glucose drink and at 30 and 120 minutes post drink. The OGTT measures the serum insulin levels at two hours (120 minutes) compared to 0 minutes. The extent of the elevation in serum insulin levels following a glucose drink are compared between baseline and the end of treatment. An increase in the elevation of serum insulin levels from baseline to the end of treatment, a positive value, indicates an improvement., Baseline (Day 1) and End of treatment (Day 85)|Change from baseline to the end of treatment in mean pro-insulin concentration., At baseline and at the end of treatment, a fasting blood sample is taken for measurement of pro-insulin concentrations. A decrease from baseline to the end of treatment, a negative value, indicates an improvement., Baseline (Day 1) and End of treatment (Day 85)|Change from baseline to the end of treatment in mean C-peptide concentration., At baseline and at the end of treatment, a fasting blood sample is taken for measurement of C-peptide concentrations. An increase from baseline to the end of treatment, a positive value, indicates an improvement., Baseline (Day 1) and End of treatment (Day 85)|Change from baseline to the end of treatment in mean beta cell function measured by Homeostasis Model Assessment 2 (HOMA2-%B)., At baseline and at the end of treatment, a fasting blood sample is taken for measurement of beta cell function calculated by HOMA2. HOMA2 is a computer model that uses fasting plasma insulin and glucose concentrations to estimate beta cell function (%B) as a percentage of a normal reference population (normal young adults). An increase from baseline to the end of treatment, a positive value, indicates an improvement., Baseline (Day 1) and End of treatment (Day 85)|Change from baseline to the end of treatment in mean Body Mass Index (BMI)., Body Mass Index (kg/m\^2) is calculated at baseline and the end of treatment. A decrease from baseline to the end of treatment, a negative value, indicates an improvement., Baseline (Day 1) and End of treatment (Day 85)|Change from baseline to the end of treatment in mean serum total cholesterol concentration., At baseline and at the end of treatment, a fasting blood sample is taken for measurement of serum total cholesterol concentrations. A decrease from baseline to the end of treatment, a negative value, indicates an improvement., Baseline (Day 1) and End of treatment (Day 85)|Change from baseline to the end of treatment in mean serum High Density Lipoprotein (HDL)-cholesterol concentration., At baseline and at the end of treatment, a fasting blood sample is taken for measurement of serum HDL-cholesterol. An increase from baseline to the end of treatment, a positive value, indicates an improvement., Baseline (Day 1) and End of treatment (Day 85)|Change from baseline to the end of treatment in mean serum triglyceride concentration., At baseline and at the end of treatment, a fasting blood sample is taken for measurement of serum triglyceride concentrations. A decrease from baseline to the end of treatment, a negative value, indicates an improvement., Baseline (Day 1) and End of treatment (Day 85)|Change from baseline to the end of treatment in mean C-reactive protein (CRP) concentration., At baseline and at the end of treatment, a fasting blood sample is taken for high sensitivity measurement of CRP concentrations. A decrease from baseline to the end of treatment, a negative value, indicates an improvement., Baseline (Day 1) and End of treatment (Day 85)|Change from baseline to the end of treatment in mean blood pressure., Blood pressure is measured at baseline and at the end of treatment. A decrease from baseline to the end of treatment, a negative value, indicates an improvement., Baseline (Day 1) and End of treatment (Day 85)|Change from baseline to the end of treatment in mean Diabetes Treatment Satisfaction Questionnaire (DTSQ): Overall Treatment Satisfaction total score., The DTSQ (status version) is a self-administered questionnaire consisting of eight items. Six of the eight items are rated from 0 (very dissatisfied, inconvenient, inflexible, etc.) to 6 (very satisfied, convenient, flexible, etc.) and are summed to produce an Overall Treatment Satisfaction score. As such, an increase from baseline to the end of treatment, a positive value, indicates an improvement., Baseline (Day 1) and End of treatment (Day 85)|Change from baseline to the end of treatment in mean Diabetes Treatment Satisfaction Questionnaire (DTSQ): Glycaemic Control total score., The DTSQ (status version) is a self-administered questionnaire consisting of eight items. Two of the eight items are used to assess 'perceived frequency of hyperglycaemia' and 'perceived frequency of hypoglycaemia', both of which are rated from 0 (none of the time) to 6 (most of the time) and are summed to produce a Glycaemic Control score. As such, a decrease from baseline to the end of treatment, a negative value, indicates an improvement., Baseline (Day 1) and End of treatment (Day 85)|Change from baseline to the end of treatment in mean overall health Visual Analogue Scale (0-100) total score., Participants are asked to assess their overall health status using a health Visual Analogue Scale (0-100), where 100 is 'the best health you can imagine' and 0 is 'the worst health you can imagine'. An increase from baseline to the end of treatment, a positive value, indicates an improvement., Baseline (Day 1) and End of treatment (Day 85)|Incidence of adverse events (AEs) as a measure of patient safety., The incidence of treatment-emergent AEs is recorded for the study duration, and the number of participants who experienced an adverse event is presented., Screening (Day -7) to Final follow-up (Day 92)|Change from baseline to the end of treatment in mean Beck Depression Inventory-II (BDI-II) total score., The BDI-II is a multiple choice self-reported inventory that is one of the most widely used instruments for measuring the severity of depression. There are 21 questions or items, each having four possible responses. Each response is assigned a score ranging from zero to three, indicating the severity of the symptom. Items 1 to 13 assess symptoms that are psychological in nature, while items 14 to 21 assess symptoms that are more physical. The sum of all BDI-II item scores indicates the severity of depression. For participants eligible for this study, a score of 21 or over represents depression. The BDI-II can distinguish between different subtypes of depressive disorders, such as major depression and dysthymia. A decrease from baseline to the end of treatment, a negative value, indicates an improvement., Baseline (Day 1) and End of treatment (Day 85)|The number of participants with a treatment-emergent flag using the Columbia-Suicide Severity Rating Scale (C-SSRS) during the course of the study., Participants are scored at each clinic visit for the following outcomes using the C-SSRS: suicidal ideation, suicidal behaviour, suicidality (including complete suicidality). Possible flags are as follows: "Wish to be Dead", "Non-specific Active Suicidal Thoughts", "Active Suicidal Ideation Without Intent", "Active Suicidal Ideation With Intent, No Plan", "Active Suicidal Ideation With Intent and Plan". The number of participants with a treatment-emergent flag is presented., Baseline (Day 1) to End of treatment (Day 85)|Incidence of hypoglycaemic episodes during the course of the study., The incidence of treatment-emergent hypoglycaemic episodes (blood glucose concentration below 3 mmol/L) is recorded for the study duration, and the number of participants who experienced a hypoglycaemic episode is presented., Screening (Day -7) to End of treatment (Day 85)|Change from baseline to the end of study in mean Cannabis Withdrawal Scale (CWS) total score., The CWS is validated and used as a diagnostic instrument in clinical and research settings where regular monitoring of withdrawal symptoms is required. The CWS will be completed for UK-based participants only. The CWS is a 19 item scale with each item (withdrawal symptom) measured on a 0-10 point scale (0 = Not at all, 5 = moderately, 10 = Extremely). For each item, the participant is asked to record the extent to which it was experienced in the last 24 hours and also to rate its negative impact on their normal daily activities (i.e., two separate scores are recorded for each item using the same 0-10 scale). Scores are summed over the 19 items for each measure, extent of experience and negative impact on normal daily activities. An increase from baseline to the end of study, a positive value, indicates withdrawal., Baseline (Day 1) and Final follow-up (Day 92)
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| Locations: |
Diabol SRL, Brasov, 500365, Romania|Nicodiab SRL, Bucuresti, 010507, Romania|Spitalul Universitar de Urgenta Militar Central "Dr. Carol Davila", Bucuresti, 010825, Romania|Institutul National de Diabet, Bucuresti, 020475, Romania|Centrul Medical 'Sanatatea Ta' SRL, Bucuresti, 020614, Romania|ArtMedical Clinic, Bucuresti, 021107, Romania|Societatea Civila Medicala dr. Paveliu, Bucuresti, 050538, Romania|Consultmed SRL, Iasi, 700547, Romania|Cabinet Medical Individual Diabet Nutritie si Boli Metabolice, Maramures, 430123, Romania|Grandmed SRL, Oradea, 410159, Romania|Spitalul Judetean de Urgente Satu Mare, Satu Mare, 440055, Romania|Spitalul Clinic Judetean de Urgenta Sibiu, Sibiu, 550245, Romania|Gagiu D. Remus Cabinet Medical Individual, Targoviste, 130083, Romania|Mediab SRL Diabet Zaharat, Targu Mures, 540142, Romania|Avondale Surgery, Chesterfield, Derbyshire, S40 4TF, United Kingdom|Hull and East Yorkshire Hospitals NHS Trust, Hull, East Yorkshire, HU3 2JZ, United Kingdom|Salford Royal NHS Foundation Trust, Salford, Greater Manchester, M6 8HD, United Kingdom|University Hospitals of Leicester NHS Trust, Leicester, Leicestershire, LE5 4QF, United Kingdom|Aintree University Hospitals NHS Foundation Trust, Liverpool, Merseyside, L9 7AL, United Kingdom|Strensall Medical Practice, York, North Yorkshire, YO32 5UA, United Kingdom|Churchill Hospital, Oxford, Oxfordshire, OX3 9DU, United Kingdom|Hathaway Surgery, Chippenham, Wiltshire, SN14 6GT, United Kingdom|Avenue Surgery, Warminster, Wiltshire, BA12 9AA, United Kingdom|St Chad's Surgery, Bath, BA3 2UH, United Kingdom|Barts and The London NHS Trust, London, E1 1BB, United Kingdom
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