Effect of Blueberries on Bone Turnover

Sponsor

Purdue University (Other)

Overall Status

Unknown status

CT.gov ID

NCT02630797

Collaborator

(none)

Enrollment

Location

Arms

30.6

Anticipated Duration (Months)

0.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study uses a bone labeling calcium tracer methodology to compare the dose-response effect of blueberry consumption on calcium retention and bone loss. Post-menopausal women will receive food or beverage products containing freeze-dried blueberries in the amount equivalent to 0.75 (low), 1.5 (medium), and 3 cups (high) of fresh blueberries per day over a 42-day period. The hypothesis is that the polyphenolics found in blueberries will reduce calcium loss from bones.

Condition or Disease	Intervention/Treatment	Phase
Osteoporosis, Postmenopausal Bone Loss, Age-related	Dietary Supplement: Blueberry Baseline Dietary Supplement: Blueberry Low Dietary Supplement: Blueberry Medium Dietary Supplement: Blueberry High	Phase 1/Phase 2

Detailed Description

Participants will be dosed with Ca-41, a rare long-lived radioisotope of calcium. After the equilibration of tracer in the body and its deposition in bones (150 days), subjects will be randomized to one of 6 dose sequences, all of which will begin with a 42-day baseline period. During baseline, 24-hour urine will be collected every 14 days. Following baseline, subjects will enter a 42-day intervention period with one of three doses of blueberries equivalent to 0.75 (low), 1.5 (medium), and 3 cups (high) of blueberries per day. Each dose will be provided in the form of freeze-dried blueberry powder incorporated in 2-4 foods or beverages per day. During the intervention, 24-hour urine will be collected weekly for 6 weeks except week 1. After intervention, subjects will enter a 42-day washout period, during which 24-hour urine will be collected every 3 weeks. The entire study duration will be 444 days for subjects who have not been dosed with Ca-41 previously. In a crossover design, all subjects will complete three 42-day intervention periods corresponding to the three doses of blueberries (low, medium, and high), each followed by a 42-day washout period. The dose-response effect of continuous blueberry consumption over a 42-day period on bone resorption in healthy post-menopausal women will be studied by measuring the loss of Ca-41 in urine by Accelerator Mass Spectrometry.

Study Design

Study Type:

Interventional

Actual Enrollment :

20 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Intervention Model Description:

This partially randomized crossover design model will include participants assigned first to a control baseline period followed by three intervention phases with a low, medium or high daily dose of blueberry products in a randomized order.This partially randomized crossover design model will include participants assigned first to a control baseline period followed by three intervention phases with a low, medium or high daily dose of blueberry products in a randomized order.

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

Berries and Bones: The Effect of Polyphenolic Metabolites From Blueberries on Bone Turnover

Actual Study Start Date :

Jan 12, 2017

Anticipated Primary Completion Date :

Jan 1, 2019

Anticipated Study Completion Date :

Aug 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Blueberry baseline No blueberry products provided as part of the usual dietary intake	Dietary Supplement: Blueberry Baseline Before the study beginning, eligible participants will receive a radioactive tracer, Ca-41, by iv infusion. A total of 150 days will be required for the equilibration of tracer in the body i.e. elimination from soft tissue and deposition in the bone. After equilibration, a baseline period of 42 days will occur, during which no blueberry products will be provided.
Active Comparator: Blueberry Low One blueberry product per day containing an equivalent of 0.75 cups of fresh blueberries provided as part of usual dietary intake for 42 days	Dietary Supplement: Blueberry Low One food or beverage product containing freeze-dried blueberry powder equivalent to 0.75 cups of fresh blueberries will be provided daily for 42 days.
Active Comparator: Blueberry Medium Two blueberry products per day containing an equivalent of 1.5 cups of fresh blueberries provided as part of usual dietary intake for 42 days	Dietary Supplement: Blueberry Medium Two food or beverage products containing freeze-dried blueberry powder equivalent to 1.5 cups of fresh blueberries will be provided daily for 42 days.
Active Comparator: Blueberry High Four blueberry products per day containing an equivalent of 3 cups of fresh blueberries provided as part of usual dietary intake for 42 days	Dietary Supplement: Blueberry High Four food or beverage products containing freeze-dried blueberry powder equivalent to 3 cups of fresh blueberries will be provided daily for 42 days.

Outcome Measures

Primary Outcome Measures

Ca-41 / Ca ratio in 24-hour urinary excretion to estimate calcium loss from bone [From the beginning of baseline (week 0) to the end of the 3rd washout period (week 42)]
Urinary Ca-41 excretion will be expressed as Ca-41/Ca ratio, which is unit-less, and converted to a percent change from the baseline value. 24-hour urine will be collected approximately every 2 weeks during baseline (week 0, 2, 4, and 6), weekly (except for week 1) during the low, medium, and high blueberry dose interventions completed in a randomized order (weeks 8-12, 20-24, 32-36) and every 3 weeks during the washout periods (weeks 15, 18, 27, 30, 39, 42). Ca-41/Ca ratios will be measured by Accelerator Mass Spectrometry.

Secondary Outcome Measures

Fasting blood and urine analysis of blueberry polyphenolic metabolites [Weeks 0, 6, 12, 18, 24, 30, 36, 42]
Polyphenol concentrations in urine and serum will be expressed in molar units and compared against reference values and across the study periods. Polyphenolic metabolites will be measured by LC-MSMS. Fasting blood and urine will be collected at the start and end of baseline (weeks 0 and 6), at the end of the low, medium, and high dose blueberry interventions (weeks 12, 24, and 36), and at the end of the 3 washout periods (weeks 18, 30, 42).
Serum and urine biochemical markers of bone metabolism: calcium concentration [Weeks 0, 6, 12, 18, 24, 30, 36, 42]
Calcium concentration in urine and serum will be expressed in mg/L and measured by Atomic Absorption Spectrophotometry. Fasting blood and urine will be collected at the start and end of baseline (weeks 0 and 6), at the end of the low, medium, and high dose blueberry interventions (weeks 12, 24, and 36), and at the end of the 3 washout periods (weeks 18, 30, 42).
Serum biochemical markers of bone metabolism: Insulin Dependent Growth Factor-1 (IGF-1) [Weeks 0, 6, 12, 18, 24, 30, 36, 42]
IGF-1 will be expressed in ng/mL and measured by ELISA. Fasting blood will be collected at the start and end of baseline (weeks 0 and 6), at the end of the low, medium, and high dose blueberry interventions (weeks 12, 24, and 36), and at the end of the 3 washout periods (weeks 18, 30, 42).
Serum biochemical markers of bone metabolism: Osteoprotegrin [Weeks 0, 6, 12, 18, 24, 30, 36, 42]
Osteoprotegerin will be expressed in pmol/L and measured by ELISA. Fasting blood will be collected at the start and end of baseline (weeks 0 and 6), at the end of the low, medium, and high dose blueberry interventions (weeks 12, 24, and 36), and at the end of the 3 washout periods (weeks 18, 30, 42).
Serum biochemical markers of bone metabolism: RANK ligand [Weeks 0, 6, 12, 18, 24, 30, 36, 42]
RANK-L will be expressed in pmol/L and measured by ELISA. Fasting blood will be collected at the start and end of baseline (weeks 0 and 6), at the end of the low, medium, and high dose blueberry interventions (weeks 12, 24, and 36), and at the end of the 3 washout periods (weeks 18, 30, 42).
Serum biochemical markers of bone metabolism: 25(OH) Vitamin D [Weeks 0, 6, 12, 18, 24, 30, 36, 42]
25(OH) Vitamin D will be expressed in ng/mL and measured by LC/MS. Fasting blood will be collected at the start and end of baseline (weeks 0 and 6), at the end of the low, medium, and high dose blueberry interventions (weeks 12, 24, and 36), and at the end of the 3 washout periods (weeks 18, 30, 42).
Serum biochemical markers of bone metabolism: Sclerostin [Weeks 0, 6, 12, 18, 24, 30, 36, 42]
Sclerostin will be expressed in ng/mL and measured by ELISA. Fasting blood will be collected at the start and end of baseline (weeks 0 and 6), at the end of the low, medium, and high dose blueberry interventions (weeks 12, 24, and 36), and at the end of the 3 washout periods (weeks 18, 30, 42).
Urine biochemical markers of bone metabolism: N-terminal telopeptide (NTX) [Weeks 0, 6, 12, 18, 24, 30, 36, 42]
NTX will be expressed in ng/mL and measured by ELISA. Fasting urine will be collected at the start and end of baseline (weeks 0 and 6), at the end of the low, medium, and high dose blueberry interventions (weeks 12, 24, and 36), and at the end of the 3 washout periods (weeks 18, 30, 42).
Serum biochemical markers of bone metabolism: procollagen I intact N-terminal (PINP) [Weeks 0, 6, 12, 18, 24, 30, 36, 42]
PINP will be will be expressed in ug/L and measured by ELISA. Fasting blood will be collected at the start and end of baseline (weeks 0 and 6), at the end of the low, medium, and high dose blueberry interventions (weeks 12, 24, and 36), and at the end of the 3 washout periods (weeks 18, 30, 42).

Eligibility Criteria

Criteria

Ages Eligible for Study:

45 Years to 70 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Female subject is healthy
Subject is > 4 years past the onset of natural menopause or total hysterectomy

Exclusion Criteria:

History of metabolic bone disease or low trauma fractures;
Subject taking osteoporosis treatment drugs or glucocorticoids within 6 months of the beginning of the study;
Subjects taking bisphosphonates within 2 years of the beginning of the study;
History of cancer, thromboembolisms, clotting disorders, uncontrolled hypertension, abnormal thyroid function, malabsorption syndrome, seizure disorders, or heart attack;
BMI > 35 kg/m2;
Subjects who will not comply with study interventions ;
Subjects who will not stop taking natural product supplements of their own selection.