CTRI Number	CTRI/2018/02/011927 [Registered on: 15/02/2018] Trial Registered Retrospectively
Last Modified On:	26/05/2020
Post Graduate Thesis	No
Type of Trial	Interventional
Type of Study	Other (Specify) [Nutrition]
Study Design	Randomized, Parallel Group, Placebo Controlled Trial
Public Title of Study Modification(s)	Effect of Almond Consumption on Blood Glucose Regulation in prediabetics
Scientific Title of Study	Effect of Almond Consumption on Blood Glucose Regulation and Cardio-Metabolic Risk Factors in Adolescents and Young Adults (16-25years) with Prediabetes
Secondary IDs if Any	Secondary ID  Registry  NIL  NIL
Details of Principal Investigator or overall Trial Coordinator (multi-center study) Modification(s)	Name  Dr Jagmeet Madan  Address  Dept of Food and Nutrition Sir Vithaldas Thackersey College of Home Science (Autonomous) SNDT Womens University,Mumbai Mumbai MAHARASHTRA 400049 India  Phone     Fax     Email  dr.jagmeetmadan@gmail.com
Details Contact Person Scientific Query Modification(s)	Name  Dr Jagmeet Madan  Address  Dept of Food and Nutrition Sir Vithaldas Thackersey College of Home Science (Autonomous) SNDT Womens University,Mumbai Mumbai MAHARASHTRA 400049 India  Phone     Fax     Email  dr.jagmeetmadan@gmail.com
Details Contact Person Public Query Modification(s)	Name  Dr Jagmeet Madan  Address  Dept of Food and Nutrition Sir Vithaldas Thackersey College of Home Science (Autonomous) SNDT Womens University,Mumbai Mumbai MAHARASHTRA 400049 India  Phone     Fax     Email  dr.jagmeetmadan@gmail.com
Source of Monetary or Material Support Modification(s)	SNDT Womens University 1, Nathibai Thackersey Road, Mumbai, Maharashtra 400020
Primary Sponsor	Name  SNDTWomens University  Address  1, Nathibai Thackersey Road, Mumbai, Maharashtra 400020  Type of Sponsor  Research institution
Details of Secondary Sponsor	Name  Address  NIL  NIL
Countries of Recruitment	India
Sites of Study Modification(s)	No of Sites = 1   Contact Person  Name of Site  Site Address  Phone/Fax/Email  Dr Jagmeet Madan  Sir VithaldasThackersey College of Home Science   Department of Food Nutrition and Dietetics SNDTWU, Juhu, Mumbai. Mumbai   9869239178 dr.jagmeetmadan@gmail.com
Details of Ethics Committee Modification(s)	No of Ethics Committees= 1   Name of Committee  Approval Status  IntersystemBiomedica Ethics Committee  Approved
Regulatory Clearance Status from DCGI	Status  Not Applicable
Health Condition / Problems Studied	Health Type  Condition  Healthy Human Volunteers  Pre-diabetes
Intervention / Comparator Agent Modification(s)	Type  Name  Details  Intervention  Almonds  20 percent of daily calorie intake of almonds given   Comparator Agent  Healthy snack   Iso-caloric healthy snack which would have similar calories as the intervention ( almonds)
Inclusion Criteria	Age From  16.00 Year(s) Age To  25.00 Year(s) Gender  Both  Details  Pre-diabetics BMI ( Asian Cutoffs) ranging from 18.5 – 30
ExclusionCriteria	Details  Chronic Energy deficiency with BMI less than 16.5 Any chronic disease eg allergies, eczema and asthma, renal disease, endocrinological problems, chronic infections, those who are on medications like steroids, diabetics
Method of Generating Random Sequence	Computer generated randomization
Method of Concealment	Not Applicable
Blinding/Masking	Open Label
Primary Outcome	Outcome  TimePoints  Improvement in pre-diabetic state- Improvement in fasting blood glucose or 2 hourly blood glucose level.  3 months
Secondary Outcome	Outcome  TimePoints  1) Insulin sensitization 2) Improvement in Lipid profile 3) Reduction in oxidized LDL 4) Reduction in inflammatory markers 5) Improvement in Quality of Life   3 months
Target Sample Size	Total Sample Size="240" Sample Size from India="240"
Phase of Trial	Phase 3
Date of First Enrollment (India)	01/09/2017
Date of First Enrollment (Global)	No Date Specified
Estimated Duration of Trial	Years="1" Months="6" Days="0"
Recruitment Status of Trial (Global) Modification(s)	Completed
Recruitment Status of Trial (India)	Closed to Recruitment of Participants
Publication Details Modification(s)	Completed statistical analysis . Working on publication
Brief Summary Modification(s)	Effect of Almond Consumption onBlood Glucose Regulation and Cardio-Metabolic Risk Factors in Adolescents and Young Adults (16-25years)with Prediabetes.  Background and study rationale  The proposed work will be a value addition to fill the lacunae in the literature regarding the effect of almond consumption on the glycemic control, body composition, cardio metabolic risk factors , inflammatory cytokines and oxidant status in adolescents suffering from prediabetes . It will be a step towards using food based approach towards prevention of non communicable diseases. The therapeutic potential to use nuts as snacks to substitute the refined carbohydrate and poor quality fat based options in the present diets of adolescents and young adults across the globe will be studied. The studies in the recent past show a rampant increase in the incidence of pre diabetes and insulin resistance in adolescents and young adults across the globe. There is a felt need to emphasize on food based approaches towards the intervention for these concerns. A dietary approach to arrest the damage early caused by these chronic non communicable diseases is of immense significance in present context .The review of literature exhibits a lacunae on the study of almond consumption on Blood glucose regulation and cardio metabolic risk factors especially in this population as majority of the published data is in adult population. The present data from India shows a large increase in the adolescent population of pre diabetes and those with two or more markers of metabolic syndrome( Anjanaetal 2011) Additionally we are also seeing a significant correlation of these concerns with the body composition of these children ranging from gross adiposity to lean adiposity ( AV Khadilkar et al 2013;  J Madan et al 2014;).The gross adiposity is seen in  adolescents and young adults who are overweight and lean adiposity is observed in adolescents and young adults who may be having low BMI or normal BMI with high body fat percentage especially visceral fat. There is data to show that the quality of diet has a direct bearing on the body composition and this cuts across all socioeconomic strata. The intake of refined carbohydrate and poor quality fat is reported to be very high in this population.  Substituting refined carbohydrates with Good Quality fats are shown to create a positive impact on the body composition and environment. Thus there is a felt need to conduct research in this area and add to the existing lacunae in the database . Study objective/hypothesis To determine the effect of almond consumption on the blood glucose regulation and cardio metabolic risk factors in adolescent and Young adults ( 16-25 years) by studying markers (Baseline and stimulated insulin and other metabolic indices, pro- & anti- inflammatory cytokines, markers of oxidant damage and antioxidants ) suffering from pre diabetes. Primary & secondary outcomes Primary outcomes: 1)      Improvement in the prediabetic state- Improvement in fasting blood glucose or 2 hourly blood glucose level. Secondary outcomes:   1)      Insulin sensitization 2)      Improvement in Lipid profile 3)      Reduction in oxidized LDL 4)      Reduction in inflammatory markers 5)      Improvement in Quality of Life    Study Design and Study Subjects The first step will be screening of target population of  Adolescentsand Young Adults (16-25years) suffering from Prediabetes. Assuming that the prevalence of prediabetes in this age group is 8 to 10 percent (Anjana et al., 2011), 1500persons from this age group will be screened. Screening of target population for identification of persons with prediabetes: One of the following criteria will be used to identify prediabetics : (i)                 Prediabetics will be defined as individuals with IFG or IGT or both. Impaired Fasting Glucose (IFG) is defined as a fasting between100 to 125mg/dL(5.6 to 6.9 mmol/L) and  2 h post-glucose value 140 to 199 mg/dL(7.8 to 11.0 mmol/L) .Impaired glucose tolerance (IGT) is defined as a 2 h post glucose between 140 to 199mg/dL. (ADA, Diabetes Care 2016, IDF, 2012)  (ii )The modality of identifying prediabetics by fasting hyperinsulinemia(≥ 20 mIU per ml) or glucose challenge hyperinsulinemia( ≥ 80mIU/ml). Hyperinsulinemia will also be defined by the ratio of fasting glucose to fasting insulin ( < 4.5)HOMA IR will be used and calculated from fasting plasma insulin (HOMA-IR=. (fasting insulin (μU/ml) X  (glucose (mmol/l)) / 22.5  2.  FPG   ( mg/dl)  X  FI   (Uu/ml) 405 ) (Hill NR, Levy JC, Matthews DR (2013).   Pre-Post, Randomized parallel design with the arm of placebo control group.Post the screening of pre-diabetic adolescents and young adults after obtaining informed consent, participants will be randomly assigned to the experimental and control groups, using random number tables. Control subjects will also be prediabetics as per the inclusion criteria. Number of subjects: 120 experimental and 120control subjects including a 10% dropout in each group. The calculation details are appended below: Sample size calculations The power in all the scenarios is taken as 80% and the confidence interval at 95%, α error at 5% (one sided for superiority) Mean difference in mmol/L in fasting glucose Sample size (evaluable sample + 10 % drop outs) 0.35 (6.3 mg/dl) 242 A defined amount of the energy(20 percent of the total calories ) consumed as a midmorning or evening /midafternoon evening snack will be substituted by almonds with supervised feeding in both intervention and control group. Participants will be allowed to follow their usual diet patterns that were followed prior to the study. The control group will be given an iso caloric snack . The snack can be a cookie /a bakery product Or a snack option which is common observation in the Indian population under consideration . This decision will be based on a pre-study assessment of the snacking pattern of the screened prediabetic population  group. Measurements at two time points : Baseline before intervention and at end of intervention:  Measurements for all participants will include weight, height, body mass index, waist circumference, waist -to - height ratio,body composition for percent body fat and visceral  fat, fasting lipid profile, oxidized LDL,Hs C-reactive protein, interleukin -6, TNF α, adiponectin, leptin. Nutrient intakes will be assessed using 24-hour diet recalls.Participants will be monitored and weekly follow ups be done to determine compliance and any problems encountered associated with the intervention. A  24-hour diet recalls will be done every week. At the end of the project, fasting blood glucose, blood glucose and insulin in response to glucose challenge test will be repeated. Also glycosylated hemoglobin will be measured before and after intervention. The duration of intervention will be 3 months. Duration of project 18 months Inclusion criteria ·         Age group 16 to 25 years ·         BMI  ( Asian Cut offs) ranging from >18.5 – 30 (Misra et al 2009) ·         Waist to Height Ratio- 0.5 (Ashwell & Gibson, BMJ Open v.6(3); 2016) ·         Pre-diabetes :    1.  Impaired Fasting Glucose (IFG) is defined as a fasting  between100 to 125mg/dL(5.6 to 6.9 mmol/L) and  2 h post-glucose value 140 to 199 mg/dL(7.8 to 11.0 mmol/L) .Impaired glucose tolerance (IGT) is defined as a 2 h post glucose between 140 to 199mg/dL. (ADA, Diabetes Care 2017, IDF, 2012)  2. Identifying pre diabetics by fasting hyperinsulinemia(≥ 20 mIU per ml) or glucose challenge hyperinsulinemia( ≥ 80mIU/ml). Hyperinsulinemia will also be defined by the ratio of fasting glucose to fasting insulin ( < 4.5) HOMA IR will be used and calculated from fasting plasma insulin ( HOMA-IR=. (fasting insulin (μU/ml) X  (glucose (mmol/l)) / 22.5  OR  FPG   ( mg/dl)  X  FI   (Uu/ml) 405 ) (Hill NR, Levy JC, Matthews DR (2013). 3. Control subjects will be those who are eu glycemic as well as a normal stimulated glucose response to 75 gm of glucose. Exclusion criteria 1.      Chronic Energy deficiency with BMI less than 16.5 2.      Any chronic disease eg allergies, eczema and asthma, renal disease, endocrinological problems, chronic infections, those who are on medications like steroids, diabetics Detailed Study Assessments: The biomarkers that will be measured are: Weight, Height, Body mass index, Waist circumference, Waist to height ratio  Body composition for percent body fat and visceral  fat,  Fasting blood glucose; Blood glucose and Insulin in response to glucose challenge test. Glycosylated hemoglobin Fasting lipid profile, oxidized LDL,  Hs C-reactive protein, interleukin -6, TNF α, adiponectin, leptin.  Assessment of nutrient intakes using 24-hour diet recalls. At the end of the project, fasting blood glucose, blood glucose and insulin in response to glucose challenge test will be repeated. Also, glycosylated hemoglobin, lipid profile and inflammatory markers will be measured before and after intervention.In addition, quality of life will be assessed using the World  Health Organization’s Quality of Life Questionnaire.  http://www.who.int/mental_health/publications/whoqol/en/ Project Description/Methodology Proposed study design: Randomized parallel design with the arm of a placebo control group. Duration of Almond consumption –3 months Quantity-.A defined amount of the energy 20 percent of the total caloriesconsumedas snacks will be substituted by almonds (supervised feeding) in two divided doses(at midmorning and evening/midafternoon)in both intervention and control group. Participants will be allowed to follow their usual diet patterns that were followed prior to the study. Experimental group will be given a snack that will provide 20 percent of the total calories from almondsthat they can consume as midmorning and evening/midafternoon snack. The control group will be given an iso- caloric snack . The snack can be a cookie /a bakery product or a snack option which is common observation in the Indianpopulation . This decision will be based on a pre-study assessment of the snacking pattern of the screened pre diabetic population to relate closely to their usual pattern.   Statistical methodology   Sampling : Purposive random sampling Sample size: We aim to have 120 participants each in the control and experimental groups at the end of the study (with 10% attrition).