Trial Plan Update. 22 th June 2015

Transcription

1 Trial Plan Update Background. MediKane has performed in house case studies on the product, NutriKane, that indicate an advantage to intestinal health, blood glucose management and inflammation states when included as part of a treatment regime. 22 th June 2015 Initial results from the ARC funded analysis project (under the ITTC scheme) indicate a positive effect on microbial populations in the intestines, as well as direct action inhibiting inflammation through the NF- KB pathways. Royal Melbourne Hospital has performed 2 independent trials including NutriKane in a treatment regime. Trial 1 involved 100 participants in recuperative care. The trial was open label pre-post comparing a new treatment regime (that included NutriKane as an integral component) vs normal care. The second trial involved 54 participants suffering from Spina Bifida and was randomised unblinded pre-post trial. Both resulted in statistically significant improvement of intestinal function measured both empirically (Bristol stool scale) and as QoL (SP36 Questionnaire). During the trials the practitioners anecdotally indicated that there was an improvement in blood glucose management in those individuals that suffered from T2DM. Independent trials held by health care practitioners have found improvements in insulin sensitivity, weight loss, inflammation states (arthritis, asthma, psoriasis), and glucose tolerance however these studies were not controlled by MediKane and are considered indicative only. This data is sufficient for MediKane to expand trials to randomised blinded trials that have statistically significant numbers of participants. Additionally MediKane intends to partner with independent bodies such as the Baker IDI institute in order to a) maintain scientific rigour; and b) improve the value of publications. Description of proposed trials and parameters. Though the results are promising, there has been insufficient numbers of particular groups and no direct causal link between proposed mechanism and observed clinical results. To address this a number of trials are underway or being prepared: 1. Fingerprinting analysis of the small molecular weight bio-active molecules using a combination of GC-MS, MS and ELISA (Conducted by Gratuk Technologies and the Macquarie University as a part of the ARC Training Centre for Molecular Technology in the Food Industry). 2. Expansion of the Glycaemic Index lowering properties of NutriKane to include all 5 basic dietary carbohydrate sources. This will be performed by Sydney University. 3. Expansion of the Glycaemic Index lowering properties of NutriKane to include blood glucose levels of T2DM subjects. This will be performed by Baker IDI. 1

2 4. A controlled, matched, single blinded open label study on the benefits to blood glucose level management observed during recuperative care This will be performed by Royal Melbourne Hospital. 5. Small scale internally controlled trials to expand on the anecdotal evidence obtained so far regarding benefits to T1DM subjects. These trials will be performed with doctor assistance to adequately monitor medication levels and collect long term HbA1c level data. 6. Expansion of small scale studies to a larger group of Type 2 diabetes individuals that have a history of trouble with BGL control. Data will be collected on standard diabetes markers as well as inflammatory cytokines and gastrointestinal microbiome species This will be conducted with Macquarie University and a clinical partner. 7. Small scale trial of the effect of NutriKane on pregnant mothers with Gestational diabetes To be arranged. 8. Where possible, blood and faecal samples will be collected from these trials for analysis of the physiological effects of NutriKane on healthy and diabetic individuals (such as TLR4 and PPARγ activation; in conjunction with Gratuk Technologies, Macquarie University and a clinical partner). 9. Large scale double blind clinical trials of the acute effects of the product on blood glucose levels to be arranged. 10. Large scale long term study on the effects of regular use of the product on glycated haemoglobin, as well as adjustment to treatment regimes, and outcomes on chronic and acute disorders associated with diabetes. This study will also make note of secondary correlating conditions such as hypertension and high cholesterol levels To be arranged. List of abbreviations: ARC- Australian Research Council BGL Blood glucose level BMI Body Mass Index GI Glycaemic Index HCP Health care professional ITTC Industrial Transformation Training Centres RMH Royal Melbourne Hospital T1DM Type 1 diabetes mellitus T2DM Type 2 diabetes mellitus 2

3 Summary of trials: # Trial description 1 Extended GI trial to cover all major carbohydrate sources Trial Status Number and type of subjects Planned and Approved 10 no BGL control issues BMI normal range Trial period Trial Type 14 days Internal control non randomised Testing parameters AS Glycemic index of foods 2 Acute BGL control with a test meal Baker IDI consult planned and agreed 36 9 days Randomised blinded crossover 1. Measure Acute increase in blood glucose levels over 2 hours (modified AS Glycemic index of foods) 2. Use dietary fibre supplement (psyllium husk) as comparator 3 BGL management in hospital ward Royal Melbourne Hospital Professor Fary Khan Recuperative care patients with T2DM or T1DM Mean time 22 days Open label single blinded randomised 1. Comparison of blood glucose levels in a controlled environment 2. Compromised patients in recuperative care 3. Inflammation and associated markers 4 T2DM Patients in Macquarie University days Internal control pre- 1. BGL log book 3

4 all 3 management groups Clinical Partner TBA post randomised double blinded 2. Inflammation markers 3. HbA1c 4. Medication changes 5. Microbiome changes 5 Type 1 patients with poor BGL control but some insulin production Planned no partner found days Internal control prepost nonrandomised 1. BGL log book 2. QoL questionnaire 3. HbA1c 4. Medication changes 6 Pregnant mothers with loss of BGL control days (or until condition alleviated) TBA 1. BGL log book 2. Medication changes 4

5 Trial 1: Expansion of Glycaemic Index lowering effect: Proposed Trial Parameters: 1: Partners: The study will be performed independently by Sydney University as part of the SUGiRS group. 2: Subjects As per Australian Standards 10 individuals with no medication requirements within Healthy BMI range. 3: Test criteria: Control: 50g glucose dissolved into 200mL water (set as 100) Test 1: 5 Basic carbohydrate groups. Test 2: Test 1 plus one sachet NutriKane D mixed with 200mL water. 4: Trial format Test taken after 12 hours fasting Baseline BGL taken just prior to consumption of meal. Meal consumed within 12 minutes BGL taken by finger-prick BGL test at 15, 30, 45, 60, 90 and 120 minutes. Area under the curve calculated and relative area to control calculated as GI 5: Scientific Rigour: Strengths: Australian standard method accepted as value around the world Independent Wide variety of food types Weaknesses: Acute measurements cannot necessarily be extrapolated to long term data Postprandial data not representative of fasting data Small numbers Healthy individuals may not represent subjects with T2DM 6: Outcomes: Expanded list of foods that have been proven to benefit from co-consumption with NutriKane D. Possible Technical note on effect. 5

6 Trial 2: acute reduction of postprandial BGL in T2DM subjects. Proposed Trial Parameters: 1: Partners: The study will be performed independently By Baker IDI under the supervision of Professor Jonathan Shaw and Dr Anne Reutens. 2: Subjects Statistically a trial is considered to be large scale when 30 individuals are present in each group. It is also estimated that the dropout rate for such a study is 10-30%. As the natural variation of subjects, and extent of observed effect are impossible to predict, power calculations do not provide useful information so subjects were set at 36 to account for 20% dropout rate. Subject selection criteria: Gender: Either Age: Group: To be finalised with consultation T2DM diet control Exclusions: To be finalised as set by Baker IDI 3: Test criteria: Control (C): Flavour and acidity regulators (natural orange oil, stevia, potassium bicarbonate, citric acid) Intervention 1 (I1): Control + psyllium husk (3.4g) as recommended as the standard dose for an individual Intervention 2 (I2): NutriKane D 4: Trial format Trial will be double blinded, all samples will be provided in unlabelled, numbered sachets. Trial is a randomised cross-over format. Subjects will be randomised to one of 6 groups: C-I1-I2 C-I2-I1 I1-C-I2 I1-I2-C I2-C-I1 I2-I1-C 6

7 Subjects will consume a test meal reflective of an actual meal as opposed to a high GI carbohydrate load (as standard for GI testing) and postprandial blood glucose levels measured every 15 minutes by finger-prick test for a 2 hour period. A washout period of 3 days will be included to prevent carryover. 5: Scientific Rigour: Strengths: Randomised Blinded Statistically significant numbers Independent Accepted standard methodology Weaknesses: Acute measurements cannot necessarily be extrapolated to long term data Postprandial data not representative of fasting data Relatively small numbers Tightly controlled group may not be representative of the general population 6: Outcomes: Professor Shaw stated and is convinced that if it can be demonstrated that NutriKane lowers the G.I. when consumed with everyday foods, it has a place in the treatment of diabetes. A positive outcome will: Convince Prof Shaw / Baker IDI that NutriKane should be used in treatment Provide a base for further trials / clinical trials by Baker IDI Result in data fit to be published in Peer Reviewed Journals Improve the life and risk profiles of both Type I and II diabetics Provide a base and reputation for future scientific and clinical trials It is important to note that the proposed trial(s) have already been conducted by MediKane, and NutriKane has been shown to definitively lower the G.I. of most foods. The trial value is therefore that this trial has been designed and overseen by Baker IDI and the results will therefore have significantly more credibility; Organisations involved will be acknowledged and highlighted by one of the foremost diabetic research and medical institutions in Australia / globally. 7

8 Trial 3: Management of BGL in T2DM patients in extended hospital stays. Proposed Trial Parameters: 1: Partners: The study will be performed independently by Royal Melbourne Hospital under the supervision of Professor Fary Khan. 2: Subjects Gender: Either Age: Any - although the ward age ranges are typically between 40 and 75 Group: Any patient that requires blood glucose management as part of their hospital care Exclusions: Hospital Ethics require consent so patients can exclude themselves. Any patient deemed unable to consume solid fibrous matter or who it is deemed will have potential handling issues will also be excluded. 3: Test criteria: Control: Patients will be matched for identical care other than NutriKane consumption Intervention 1: One of the currently available fibre options (Metamucil or Benefiber). Intervention 2: NutriKane D 4: Trial format Specific format will be determined by RMH as per hospital policy however general format as follows: Patients admitted for recuperative care will be placed onto a standard diet and exercise regime for their condition. Patients will be matched for age, gender, BMI, medication, regime and then placed into one of three groups: 1) no additional fibre consumption; 2) current fibre supplement; 3) NutriKane D. Level of blood glucose control will be monitored using standard hospital measures. Patients will be given instructions on how to continue regime after discharge and followed up at 3 months to determine follow on benefit. 5: Scientific Rigour: Strengths: Controlled environment Possibility for single blinded study 8

9 Statistically significant numbers Independent Measures both in house and uncontrolled environmental parameters Weaknesses: Non-randomised Compromised patients may not be representative of the general population Relatively small numbers 6: Outcomes: Allow the hospital to officially name NutriKane D to be used in treatment of individuals with blood glucose management issues Improve the reputation / visibility of NutriKane D to Australian Hospitals Result in data fit to be published in Peer Reviewed journals Improve the hospital stay of people with T1DM and T2DM. 9

10 Trial 4: Randomised, blinded lifestyle control study for T2DM subjects: Proposed Trial Parameters: 1: Partners: The study will be performed by Gratuk Technologies on behalf of MediKane and with Macquarie University as a part of the ARC ITTC program (Training Centre for Molecular Technology in the Food Industry). A clinical partner is yet to be selected, but several have been approached and expressed interest. 2: Subjects This trial is intended to expand the case study work performed so far. As the results have been universally positive, the study shall be inclusive of all three major groups diet control only, diet control plus oral medication, and diet control, oral medication and exogenous insulin. The trial will include at least 36 subjects, however may be expanded to 36 subjects in each sub group if required. Subject selection criteria: Gender: Either Age: not limited Group: T2DM using diet control, oral medication, and exogenous insulin Exclusions: unable to be on a high potassium diet due to medication or hyperkalaemia. Significant intestinal health issues that require specific medication. Antibiotic use. 3: Test criteria: Control: Diet and exercise control period pre-intervention Intervention 1: Psyllium husk (3.4g) as recommended as the standard dose for an individual Intervention 2: NutriKane D 4: Trial format Trial is to be Lifestyle based, as there is ample evidence that tightly controlled diet and exercise intervention studies to not accurately reflect patient results in the real world. Trial will be double blinded, all samples will be provided in unlabelled, numbered sachets. Trial is a randomised cross-over format. Subjects will be managed by physicians that will monitor all health factors and make changes as per normal procedures. 10

11 Blood will be sampled at baseline and tested for standard diabetes health markers as well as CRP, a 45 cytokine array and liver function. Data will be compared with historical data from doctor-patient interaction to establish if any recent changes have had significant impact of management regime. At baseline, faecal samples will also be collected to calculate microbiome populations. For the duration of the study the subject will use an expanded log book to make note of levels and type of food and alcohol consumption as well as amount and intensity of exercise. Subjects will be placed onto a managed regime for 90 days and changes in markers observed. Subjects will then be randomised to either intervention 1 or intervention 2 and the process repeated. Faecal samples will be collected at 2, 5, 14 and 90 days as microbial populations change faster than blood markers. Subjects will then cross over to the other intervention and the process repeated. 5: Scientific Rigour: Strengths: Randomised Double blinded neither HCP nor subject will know which intervention is in use. Statistically significant numbers Lifestyle based more reflective of typical use than a controlled clinical trial Semi independent as doctors will control patient use and be unbiased towards NutriKane Weaknesses: Inherent variability may prove too much to obtain significant results Long study time may result in higher dropout rate Relatively small numbers 6: Outcomes: Statistically significant data that may be used as the basis of future claims Gateway for decision for NutriKane to begin TGA registration Indicative data on NutriKane ability to reduce dependence on medication Direct biochemical link to potential mechanisms Several Peer Reviewed publications 3 PhD candidates Launching point for next ARC grant Indicative evidence for further treatment options (inflammation etc.) for NutriKane 11

12 Trial 5 Expansion of data on the benefits of NutriKane to T1DM: Proposed Trial Parameters: 1: Partners: HCPs that MediKane has previously worked with. 2: Subjects This trial is intended to expand the case study work performed so far. To date results have been largely uncontrolled the purpose of this study is to increase control of case studies to determine if randomised controls are warranted. Subject selection criteria: Gender: Either Age: not limited Group: T1DM with some pancreatic activity remaining Exclusions: unable to be on a high potassium diet due to medication or hyperkalaemia. Significant intestinal health issues that require specific medication. Insulin pump. 3: Test criteria: Control: previous history Intervention 1: NutriKane D 4: Trial format Trial is to be Lifestyle based, as there is ample evidence that tightly controlled diet and exercise intervention studies to not accurately reflect patient results in the real world. Trial will be open label non-blinded pre-post format. Trial is non-randomised. Subjects will be managed by HCP that will monitor all health factors and make changes as per normal procedures. Blood will be sampled at baseline and tested for standard diabetes health markers. Data will be compared with historical data from doctor-patient interaction to establish if any recent changes have had significant impact of management regime. For the duration of the study the subject will use an expanded log book to make note of levels and type of food and alcohol consumption, as well as amount and intensity of exercise. Subjects placed on intervention for 90 days and parameters re-tested. 12

13 5: Scientific Rigour: Strengths: Lifestyle based more reflective of typical use than a controlled clinical trial Semi independent as doctors will control patient use and be unbiased towards NutriKane Weaknesses: Small numbers Long study time may result in higher dropout rate Non-randomised Non-blinded Control may not accurately reflect pre-intervention status 6: Outcomes: Indicative data to determine if larger scale randomised trials are warranted. Depending on quality of data and quantum of changes observed may warrant publication in Peer Reviewed journal. 13

14 Trial 6 Indicative trial to measure benefits to pregnant women: Proposed Trial Parameters: 1: Partners: HCPs that MediKane has previously worked with. 2: Subjects This trial is intended to investigate the benefits that NutriKane D can have to pregnant women. There is varying levels of evidence that NutriKane D may help in several areas regularity, reflux and blood glucose control. To date nothing more than anecdotal data has been recorded. Subject selection criteria: Gender: Female Age: not limited Group: pregnant women experiencing loss of BGL management control after the first trimester. Exclusions: unable to be on a high potassium diet due to medication or hyperkalaemia. Significant intestinal health issues that require specific medication. Hypersensitivity. Any diabetes medication prescription. 3: Test criteria: Control: none Intervention 1: NutriKane D 4: Trial format Trial will be open label. Trial is non-randomised. Subjects will be managed by HCP that will monitor all health factors and make changes as per normal procedures. For the duration of the study the subject will use an expanded log book to make note of levels and type of food and alcohol consumption, as well as reflux and constipation events. Acute blood glucose levels will be monitored by finger-prick test. 5: Scientific Rigour: Strengths: Semi independent as doctors will control patient use and be unbiased towards NutriKane Weaknesses: Small numbers 14

15 Non-randomised Non-blinded External factors not accounted for 6: Outcomes: Indicative data to determine if larger scale randomised trials are warranted. 15