Clinical trial NCT02630797: Effect of Blueberries on Bone Turnover
Official title: Berries and Bones: The Effect of Polyphenolic Metabolites From Blueberries on Bone Turnover
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Osteoporosis, Postmenopausal
Bone Loss, Age-related
Keywords: Bone Health
Calcium
Osteoporosis
Polyphenolics
Lead sponsor: Purdue University
Sponsor class: OTHER
First posted: 2015-12-15
Enrollment: 20
Sex: FEMALE
Minimum age (years): 45
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
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.
Primary purpose: PREVENTION

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.

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.

Primary outcomes:
measure: Ca-41 / Ca ratio in 24-hour urinary excretion to estimate calcium loss from bone
timeFrame: From the beginning of baseline (week 0) to the end of the 3rd washout period (week 42)
Secondary outcomes:
measure: Fasting blood and urine analysis of blueberry polyphenolic metabolites
timeFrame: Weeks 0, 6, 12, 18, 24, 30, 36, 42
measure: Serum and urine biochemical markers of bone metabolism: calcium concentration
timeFrame: Weeks 0, 6, 12, 18, 24, 30, 36, 42
measure: Serum biochemical markers of bone metabolism: Insulin Dependent Growth Factor-1 (IGF-1)
timeFrame: Weeks 0, 6, 12, 18, 24, 30, 36, 42
measure: Serum biochemical markers of bone metabolism: Osteoprotegrin
timeFrame: Weeks 0, 6, 12, 18, 24, 30, 36, 42
measure: Serum biochemical markers of bone metabolism: RANK ligand
timeFrame: Weeks 0, 6, 12, 18, 24, 30, 36, 42
measure: Serum biochemical markers of bone metabolism: 25(OH) Vitamin D
timeFrame: Weeks 0, 6, 12, 18, 24, 30, 36, 42
measure: Serum biochemical markers of bone metabolism: Sclerostin
timeFrame: Weeks 0, 6, 12, 18, 24, 30, 36, 42
measure: Urine biochemical markers of bone metabolism: N-terminal telopeptide (NTX)
timeFrame: Weeks 0, 6, 12, 18, 24, 30, 36, 42
measure: Serum biochemical markers of bone metabolism: procollagen I intact N-terminal (PINP)
timeFrame: Weeks 0, 6, 12, 18, 24, 30, 36, 42
Other outcomes:
Locations:
city: West Lafayette
country: United States
facility: Department of Nutrition Science Purdue University
state: Indiana
Study officials:
affiliation: Department of Nutrition Science, Purdue University
name: Connie M Weaver, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.