To Investigate the Impact of a Nutritional Supplement on Bone Turnover Markers in Indian Healthy Premenopausal Women (25- 45 Years) After 6 Months of Intervention

Study Overview
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Brief Summary
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To investigate the effect of nutritional supplement on bone turnover markers (which are sensitive and respond quickly to nutrition or drug intervention) in Indian healthy premenopausal women after 6 months of intervention.

Detailed Description
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This will be a double blind, single-center, randomized-controlled trial testing the effect of fortified beverage on bone turnover markers as compared to placebo control in 25-45 years old premenopausal women. The study will consist of two groups: Group 1 (Test) - Protein rich beverage powder fortified with MMN and Group 2 (control) - Low protein non-fortified iso-caloric beverage powder.

Official Title
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Impact of a Nutritional Supplement on Bone Turnover Markers in Indian Healthy Premenopausal Women (25-45 Yrs; Inclusive) After 6 Months of Intervention: a Randomised Double Blind Controlled Trial

Conditions
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Growth and Development

Intervention / Treatment
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* Dietary Supplement: Fortified Beverage Powder
* Dietary Supplement: Non fortified beverage Powder


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Demonstrates understanding of the study procedures, restrictions and willingness to participate as evidenced by voluntary written informed consent and has received a signed and dated copy of the informed consent form. Female Participants. Good general and mental health with, in the opinion of the investigator or medically qualified designee no clinically significant and relevant abnormalities in medical history or upon physical examination. BMI between 18.0-30 (kg/m2, Kilograms Per Meter Square) inclusive. Women who understand, willing, able and likely to comply with all study procedures and restrictions. Exclusion Criteria: Women who are known to be pregnant or who are intending to become pregnant over the duration of the study or Women who have a positive urine pregnancy test. Women who have attained physiological menopause defined as those who have not had a menstrual period for consecutive 12 months. Women who are breast-feeding. Current (within 14 days of the start of the study) or regular use of any prescription, over the counter (OTC), vitamin supplements herbal medicine unless the medication has been approved by the study physician. Treatment with bisphosphonates (any dose within the previous 2 years) or other medications known to affect bone (within the previous 6 months). History of metabolic bone disease. Any hormonal disorders or disturbances. Bone fracture in last 12 months. Known or suspected intolerance or hypersensitivity to the study materials (or closely related compounds) or any of their stated ingredients. Participant is lactose intolerant. Participation in another clinical study (including cosmetic studies) or receipt of an investigational drug within 30 days of the screening visit. Previous participation in this study. Recent history (within the last 1 year) of alcohol or other substance abuse. More than 2 Units of alcohol per day Smokers Currently taking any other health food drinks/beverages or supplements (including nutritional supplements e.g. multivitamins and/or herbal supplements e.g. ginkgo) or has been on supplements within a month prior to study start. Women who used medication known to influence bone mass and the use of calcium, vitamin D, and multivitamin supplements on a regular basis were stopped 2 months before the onset of the trial. An employee of the sponsor or the study site or members of their immediate family. Ongoing conditions known to cause abnormalities of calcium metabolism or skeletal health, malabsorption syndromes (such as coeliac or Crohn's disease), hyperthyroidism, hyperparathyroidism, hypo- or hypercalcaemia, osteomalacia, Paget's disease, and diabetes. Fracture in the past 12 months. Known chronic kidney disease or alcoholism. Obesity women ( Body Mass Index, BMI>30) and Thinness i.e. BMI<18 kg/m2 Severely anemic (Hemoglobin, Hb<8 g/dl, Grams Per Decilitre). Undertaking excessive exercise (>2 strenuous* exercise sessions per week) Contraceptive injections within the previous year. Known histories of surgeries such as bilateral oophrectomy (surgical removal of ovaries) Diagnosed hypogondal states such as Turner syndrome, Klinfelter syndrome, Kallman syndrome, anorexia nervosa, hypothalamic amenorrhea or hyperprolactinemia Hemotological disorders e.g. Hemophilia, Leukemia and lymphomas monoclonal multiple myeloma, sickle cell disease, Thalassemia etc. Rheumatological and autoimmune disorders such as ankylosing spondylitis, rheumatoid arthritis, systemic lupus etc. Miscellaneous conditions and diseases such as Human Immunodeficiency Virus/acquired immunodeficiency syndrome (HIV/AIDS), alcoholism, amyloidosis, chronic metabolic acidosis, Chronic Obstructive Pulmonary Disease (COPD), congestive heart failure, depression etc.

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1- Protein rich beverage powder fortified with MMN<br>Participants will be administered orally two doses of cereal based fortified beverage (30 grams powder made up in 200 milliliter (mL) water) daily in the morning and evening for 6 months. | Dietary Supplement: Fortified Beverage Powder<br>* The tumbler will be filled with water up to the 200 mL mark. The entire contents of one sachet (Fortified beverage powder) will be gradually emptied in the tumbler with intermittent stirring to avoid formation of lumps. The reconstituted product will be consumed by the participants immediately orally.<br>|
| Other: Group 2 -Low protein non-fortified iso-caloric beverage powder<br>Participants will be administered orally two doses (in morning and evening) of low protein non fortified isocaloric beverage (30 grams powder made up in 200 mL water) daily for 6 months. | Dietary Supplement: Non fortified beverage Powder<br>* The tumbler will be filled with water up to the 200 mL mark. The entire contents of one sachet (Non fortified beverage powder) will be gradually emptied in the tumbler with intermittent stirring to avoid formation of lumps. The reconstituted product will be consumed by the participants immediately orally.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Serum Cross Linking C-telopeptide of Type 1 Collagen (s-CTX-1) at 6 Months | s-CTX-1 is a bone resorption marker which is used to assess the bone health. After 6 months of taking the allocated product, blood sample was collected under 12-hour fasting condition. Blood serum of whole blood collected from each participant was then isolated by the method of centrifugation. CTX-1 serum was analysed using biochemical tests from the samples stored. Decreased s-CTX-1 is associated with improved bone health. | At baseline and at 6 months | 
| Change From Baseline in the Ratio of Carboxylated (c-OC) to Under-carboxylated Osteocalcin (Uc-OC) at 6 Months | c-OC/ uc-OC is considered as a surrogate marker of bone formation which is used to assess the bone health. After 6 months of taking the allocated product, blood sample was collected under 12-hour fasting condition. Blood serum of whole blood collected from each participant was then isolated by the method of centrifugation. c-OC/ uc-OC levels were analysed using biochemical tests from the samples stored. Increased c-OC/ uc-OC is associated with improved bone health. | At baseline and 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Serum Cross Linking C-telopeptide of Type 1 Collagen (s-CTX-1) at 3 Months | s-CTX-1 is a bone resorption marker which is used to assess the bone health. After 3 months of taking the allocated product, blood sample was collected under 12-hour fasting condition. Blood serum of whole blood collected from each participant was then isolated by the method of centrifugation. CTX-1 serum was analysed using biochemical tests from the samples stored. Decreased s-CTX-1 is associated with improved bone health. | At baseline and at 3 months | 
| Change From Baseline in the Ratio of Carboxylated (c-OC) to Under-carboxylated Osteocalcin (Uc-OC) at 3 Months | c-OC/ uc-OC is considered as a surrogate marker of bone formation which is used to assess the bone health. After 3 months of taking the allocated product, blood sample was collected under 12-hour fasting condition. Blood serum of whole blood collected from each participant was then isolated by the method of centrifugation. c-OC/ uc-OC levels were analysed using biochemical tests from the samples stored. Increased c-OC/ uc-OC is associated with improved bone health. | At baseline and at 3 months | 
| Change From Baseline in Urinary Cross Linking C-telopeptide of Type 1 Collagen at 3 Months and 6 Months | Urinary-CTX-1 is a bone resorption surrogate marker which is used to assess the bone health. After 3 months and 6 months of taking the allocated product, spot urinary sample were collected. CTX-1 urine levels were analysed using biochemical tests from the samples stored. Decreased urinary CTX-1 is associated with improved bone health. | At baseline, at 3 and 6 months | 
| Change From Baseline in Serum N-terminal Telopeptide of Type 1 Collagen (s-NTX-1) at 3 Months and 6 Months | NTX-1 is a bone resorption surrogate marker which is used to assess the bone health. After 3 months and 6 months of taking the allocated product, blood sample was collected under 12-hour fasting condition. Blood serum of whole blood collected from each participant was then isolated by the method of centrifugation. NTX-1 serum was analysed using biochemical tests from the samples stored. Decreased s-NTX-1 is associated with improved bone health. The unit of measurement is nanomole bone collagen equivalent (NM BCE). | At baseline, at 3 months and 6 months | 
| Change From Baseline in Serum Procollagen Type 1 N-terminal Propeptide (s-P1NP) at 3 Months and 6 Months | P1NP is a bone formation surrogate marker which is used to assess the bone health being the most abundant protein of bone matrix. After 3 months and 6 months of taking the allocated product, blood sample was collected under 12-hour fasting condition. Blood serum of whole blood collected from each participant was then isolated by the method of centrifugation. P1NP serum was analysed using biochemical tests from the samples stored. Increased s-P1NP is associated with improved bone health. | At baseline, at 3 months and 6 months | 
| Change From Baseline in Bone Specific Alkaline Phosphatase (BSAP) at 3 Months and 6 Months | BSAP is a bone formation surrogate marker which is used to assess the bone health. After 3 months and 6 months of taking the allocated product, blood sample was collected under 12-hour fasting condition. Blood serum of whole blood collected from each participant was then isolated by the method of centrifugation. BSAP serum was analysed using biochemical tests from the samples stored. Increased s-BSAP is associated with improved bone health. | At baseline, at 3 months and 6 months | 
| Change From Baseline in Serum Parathyroid Hormone (s-PTH) at 3 Months and 6 Months | PTH is used to compare calcium concentration status which defines the healthy bones. Intact PTH is the biologically active form and is secreted when the calcium level is low. After 3 months and 6 months of taking the allocated product, blood sample was collected under 12-hour fasting condition. Blood serum of whole blood collected from each participant was then isolated by the method of centrifugation. PTH serum was analysed using biochemical tests from the samples stored. Decreased s-PTH is associated with improved bone health. | At baseline, at 3 months and 6 months | 
| Change From Baseline in Urinary Calcium at 3 Months and 6 Months | Urinary calcium is used to compare calcium concentration status which defines the healthy bones. After 3 months and 6 months of taking the allocated product, spot urinary sample were collected. Urinary calcium was analysed using biochemical tests from the samples stored. Decreased urinary calcium is associated with improved bone health. | At baseline, at 3 months and 6 months | 
| Change From Baseline in Serum Calcium at 3 Months and 6 Months | Serum calcium is used to compare calcium concentration status which defines the healthy bones. After 3 months and 6 months of taking the allocated product, blood sample was collected under 12-hour fasting condition. Blood serum of whole blood collected from each participant was then isolated by the method of centrifugation. Serum calcium was analysed using biochemical tests from the samples stored. Increased serum calcium is associated with improved bone health. | At baseline, at 3 months and 6 months | 
| Change From Baseline in Serum Phosphorus at 3 Months and 6 Months | Serum phosphorus is a diagnostic marker for assessment of healthy bones. After 3 months and 6 months of taking the allocated product, blood sample was collected under 12-hour fasting condition. Blood serum of whole blood collected from each participant was then isolated by the method of centrifugation. Serum phosphorus was analysed using biochemical tests from the samples stored. Increased serum phosphorus is associated with improved bone health. | At baseline, at 3 months and 6 months | 
| Change From Baseline in Total Alkaline Phosphatase (ALP) at 3 Months and 6 Months | ALP is a diagnostic marker of which is used to assess bone mineral density for assessment of healthy bones. After 3 months and 6 months of taking the allocated product, blood sample was collected under 12-hour fasting condition. Blood serum of whole blood collected from each participant was then isolated by the method of centrifugation. Serum ALP was analysed using biochemical tests from the samples stored. Increased serum ALP is associated with improved bone health. | At baseline, at 3 months and 6 months | 
| Change From Baseline in Serum Vitamin D3 Using 25-hydroxycholecalciferol (25 OH D3) at 3 Months and 6 Months | Serum vitamin-D3 is used to analyse the status of vitamin-D profile which is necessary for healthy bones. The marker used for analyzing serum vitamin-D3 was 25 OH D3. After 3 months and 6 months of taking the allocated product, blood sample was collected under 12-hour fasting condition. Blood serum of whole blood collected from each participant was then isolated by the method of centrifugation. Serum vitamin-D3 was analysed using biochemical tests from the samples stored. Increased serum vitamin-D3 is associated with improved bone health. | At baseline, at 3 months and 6 months | 
| Change From Baseline in Serum Selenium (Se) at 3 Months and 6 Months | Serum Se is used to assess the status of micronutrient profile necessary for healthy bones. After 3 months and 6 months of taking the allocated product, blood sample was collected under 12-hour fasting condition. Blood serum of whole blood collected from each participant was then isolated by the method of centrifugation. Serum Se was analysed using biochemical tests from the samples stored. Increased serum Se is associated with improved bone health. | At baseline, at 3 months and 6 months | 
| Change From Baseline in Plasma Zinc (Zn) at 3 Months and 6 Months | Plasma Zn is used to assess the status of micronutrient profile necessary for healthy bones. After 3 months and 6 months of taking the allocated product, blood sample was collected under 12-hour fasting condition. Blood serum of whole blood collected from each participant was then isolated by the method of centrifugation. Plasma Zn was analysed using biochemical tests from the samples stored. Increased plasma Zn is associated with improved bone health. | At baseline, at 3 months and 6 months | 
| Change From Baseline in Serum Folic Acid (Folate) at 3 Months and 6 Months | Serum folic acid (folate) is used to assess the status of micronutrient profile necessary for healthy bones. After 3 months and 6 months of taking the allocated product, blood sample was collected under 12-hour fasting condition. Blood serum of whole blood collected from each participant was then isolated by the method of centrifugation. Plasma Zn was analysed using biochemical tests from the samples stored. Increased serum folate is associated with improved bone health. | At baseline, at 3 months and 6 months | 
| Change From Baseline in Plasma Vitamin-B6 at 3 Months and 6 Months | Plasma vitamin-B6 is used to assess the status of micronutrient profile necessary for healthy bones. After 3 months and 6 months of taking the allocated product, blood sample was collected under 12-hour fasting condition. Blood serum of whole blood collected from each participant was then isolated by the method of centrifugation. Plasma vitamin-B6 was analysed using biochemical tests from the samples stored. Increased plasma vitamin-B6 is associated with improved bone health. | At baseline, at 3 months and 6 months | 
| Change From Baseline in Serum Vitamin-B12 at 3 Months and 6 Months | Serum vitamin-B12 is used to assess the status of micronutrient profile necessary for healthy bones. After 3 months and 6 months of taking the allocated product, blood sample was collected under 12-hour fasting condition. Blood serum of whole blood collected from each participant was then isolated by the method of centrifugation. Serum vitamin-B12 was analysed using biochemical tests from the samples stored. Increased serum vitamin-B12 is associated with improved bone health. | At baseline, at 3 months and 6 months |