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Effect of Blueberries on Bone Turnover

Primary Purpose

Osteoporosis, Postmenopausal, Bone Loss, Age-related

Status
Unknown status
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Blueberry Baseline
Blueberry Low
Blueberry Medium
Blueberry High
Sponsored by
Purdue University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Osteoporosis, Postmenopausal focused on measuring Bone Health, Calcium, Osteoporosis, Polyphenolics

Eligibility Criteria

45 Years - 70 Years (Adult, Older Adult)FemaleAccepts Healthy Volunteers

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.

Sites / Locations

  • Department of Nutrition Science Purdue University

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Placebo Comparator

Active Comparator

Active Comparator

Active Comparator

Arm Label

Blueberry baseline

Blueberry Low

Blueberry Medium

Blueberry High

Arm Description

No blueberry products provided as part of the usual dietary intake

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

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

Four blueberry products per day containing an equivalent of 3 cups of fresh blueberries provided as part of usual dietary intake for 42 days

Outcomes

Primary Outcome Measures

Ca-41 / Ca ratio in 24-hour urinary excretion to estimate calcium loss from bone
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
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
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)
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
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
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
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
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)
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)
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).

Full Information

First Posted
December 7, 2015
Last Updated
May 2, 2018
Sponsor
Purdue University
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1. Study Identification

Unique Protocol Identification Number
NCT02630797
Brief Title
Effect of Blueberries on Bone Turnover
Official Title
Berries and Bones: The Effect of Polyphenolic Metabolites From Blueberries on Bone Turnover
Study Type
Interventional

2. Study Status

Record Verification Date
May 2018
Overall Recruitment Status
Unknown status
Study Start Date
January 12, 2017 (Actual)
Primary Completion Date
January 2019 (Anticipated)
Study Completion Date
August 2019 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Purdue University

4. Oversight

Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Osteoporosis, Postmenopausal, Bone Loss, Age-related
Keywords
Bone Health, Calcium, Osteoporosis, Polyphenolics

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 1, Phase 2
Interventional Study Model
Crossover Assignment
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.
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
20 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Blueberry baseline
Arm Type
Placebo Comparator
Arm Description
No blueberry products provided as part of the usual dietary intake
Arm Title
Blueberry Low
Arm Type
Active Comparator
Arm Description
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
Arm Title
Blueberry Medium
Arm Type
Active Comparator
Arm Description
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
Arm Title
Blueberry High
Arm Type
Active Comparator
Arm Description
Four blueberry products per day containing an equivalent of 3 cups of fresh blueberries provided as part of usual dietary intake for 42 days
Intervention Type
Dietary Supplement
Intervention Name(s)
Blueberry Baseline
Intervention Description
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.
Intervention Type
Dietary Supplement
Intervention Name(s)
Blueberry Low
Intervention Description
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.
Intervention Type
Dietary Supplement
Intervention Name(s)
Blueberry Medium
Intervention Description
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.
Intervention Type
Dietary Supplement
Intervention Name(s)
Blueberry High
Intervention Description
Four food or beverage products containing freeze-dried blueberry powder equivalent to 3 cups of fresh blueberries will be provided daily for 42 days.
Primary Outcome Measure Information:
Title
Ca-41 / Ca ratio in 24-hour urinary excretion to estimate calcium loss from bone
Description
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.
Time Frame
From the beginning of baseline (week 0) to the end of the 3rd washout period (week 42)
Secondary Outcome Measure Information:
Title
Fasting blood and urine analysis of blueberry polyphenolic metabolites
Description
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).
Time Frame
Weeks 0, 6, 12, 18, 24, 30, 36, 42
Title
Serum and urine biochemical markers of bone metabolism: calcium concentration
Description
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).
Time Frame
Weeks 0, 6, 12, 18, 24, 30, 36, 42
Title
Serum biochemical markers of bone metabolism: Insulin Dependent Growth Factor-1 (IGF-1)
Description
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).
Time Frame
Weeks 0, 6, 12, 18, 24, 30, 36, 42
Title
Serum biochemical markers of bone metabolism: Osteoprotegrin
Description
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).
Time Frame
Weeks 0, 6, 12, 18, 24, 30, 36, 42
Title
Serum biochemical markers of bone metabolism: RANK ligand
Description
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).
Time Frame
Weeks 0, 6, 12, 18, 24, 30, 36, 42
Title
Serum biochemical markers of bone metabolism: 25(OH) Vitamin D
Description
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).
Time Frame
Weeks 0, 6, 12, 18, 24, 30, 36, 42
Title
Serum biochemical markers of bone metabolism: Sclerostin
Description
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).
Time Frame
Weeks 0, 6, 12, 18, 24, 30, 36, 42
Title
Urine biochemical markers of bone metabolism: N-terminal telopeptide (NTX)
Description
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).
Time Frame
Weeks 0, 6, 12, 18, 24, 30, 36, 42
Title
Serum biochemical markers of bone metabolism: procollagen I intact N-terminal (PINP)
Description
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).
Time Frame
Weeks 0, 6, 12, 18, 24, 30, 36, 42

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
45 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Connie M Weaver, PhD
Organizational Affiliation
Department of Nutrition Science, Purdue University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Nutrition Science Purdue University
City
West Lafayette
State/Province
Indiana
ZIP/Postal Code
47907-2059
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
20499363
Citation
Chen JR, Lazarenko OP, Wu X, Kang J, Blackburn ML, Shankar K, Badger TM, Ronis MJ. Dietary-induced serum phenolic acids promote bone growth via p38 MAPK/beta-catenin canonical Wnt signaling. J Bone Miner Res. 2010 Nov;25(11):2399-411. doi: 10.1002/jbmr.137.
Results Reference
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PubMed Identifier
18328688
Citation
Devareddy L, Hooshmand S, Collins JK, Lucas EA, Chai SC, Arjmandi BH. Blueberry prevents bone loss in ovariectomized rat model of postmenopausal osteoporosis. J Nutr Biochem. 2008 Oct;19(10):694-9. doi: 10.1016/j.jnutbio.2007.09.004. Epub 2008 Mar 6.
Results Reference
background
PubMed Identifier
19584189
Citation
Weaver CM, Martin BR, Jackson GS, McCabe GP, Nolan JR, McCabe LD, Barnes S, Reinwald S, Boris ME, Peacock M. Antiresorptive effects of phytoestrogen supplements compared with estradiol or risedronate in postmenopausal women using (41)Ca methodology. J Clin Endocrinol Metab. 2009 Oct;94(10):3798-805. doi: 10.1210/jc.2009-0332. Epub 2009 Jul 7.
Results Reference
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Effect of Blueberries on Bone Turnover

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