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Dried Plums and Bone Health in Postmenopausal Women

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ClinicalTrials.gov Identifier: NCT02822378
Recruitment Status : Recruiting
First Posted : July 4, 2016
Last Update Posted : December 20, 2018
Sponsor:
Collaborator:
California Dried Plum Board
Information provided by (Responsible Party):
Mary Jane DeSouza, Penn State University

Brief Summary:
Postmenopausal women often seek non-pharmacologic interventions for the protection of bone health. Previous research in humans and rodents has indicated that dietary dried plum consumption may be beneficial for bone health, especially in postmenopausal women. However, it is unknown in what quantity dried plums need to be consumed to be of benefit and through what mechanisms dried plums act to impact bone health. Therefore, the purpose of this study is to evaluate the impact of 52 weeks of dried plums consumption in varying quantities on bone mineral density (BMD), bone geometry, and estimated bone strength in postmenopausal women. The investigators also seek to evaluate the mechanisms underlying the effects of dried plums as a dietary supplement by assessing polyphenols and the bioavailable conjugated metabolites in the urine of postmenopausal women taking different doses of dietary dried plums. The investigators aim to further investigate the mechanisms of dried plum action on bone by measuring markers of bone metabolism in response to dried plum consumption.

Condition or disease Intervention/treatment Phase
Postmenopausal Osteoporosis Dietary Supplement: Dried Plum Dietary Supplement: Calcium supplement Dietary Supplement: Vitamin D supplement Not Applicable

Detailed Description:

Given the current high incidence of osteoporosis, reducing the risk of osteoporosis development is essential. Recent estimates, based on the 2010 US Census, indicate that approximately 10.3 million people age 50 and older have osteoporosis. By 2030 the prevalence of osteoporosis for women 50 years and older is projected to reach 13.6 million. Postmenopausal osteoporosis is characterized not only by hypoestrogenism, but also by increased production of reactive oxygen species, oxidative stress, and inflammatory response. Current first line strategies are treatment of osteoporosis with pharmacologic approaches. Complementary recommendations include the maintenance of calcium (Ca2+) and vitamin D (VitD) intake to meet the current recommendations. Although the anti-resorptive therapies are effective they are also associated with an array of negative side effects, which reduce patient compliance to use of the therapy.

Non-pharmacologic options to reducing the risk of bone loss are becoming more attractive to many postmenopausal women. The phenolics and bioavailable conjugated metabolites found in dried plums are proposed to modulate the inflammatory signaling pathways and have the potential to influence bone formation and bone resorption, thus modulating the risk of bone loss. The investigators are conducting a 52 week dose ranging randomized controlled trial that builds upon previous rodent and human work and addresses the experimental design limitations of the previous work, to assess bone outcomes with clinical (BMD) and mechanistic (bone geometry, bone metabolism markers, and inflammation markers) techniques. Additionally, this study will include a detailed assessment of the phenolics in the dried plums to explore the relationship between these compounds and bone outcomes.

Participants will participate in a 1-2 week screening period followed by a 1-2 week baseline period. At the end of baseline randomization to 1 of 3 groups will occur (Ca2+ and VitD only; 50g Dried Plums/day and Ca2+ and VitD; 100g Dried Plums/day and Ca2+ and VitD). Dried plums and Calcium/Vitamin D supplements will be provided to participants for the duration of the intervention. At the beginning of the 52 week intervention participants will begin consumption of dried plums and will be given a run in period where the number of dried plums consumed per day increases slowly to minimize the side effects felt by the participants. The dried plums will be consumed as snacks in the morning, midday, and in the evening. Participants will visit the laboratory for testing every 4 weeks during the 52 week intervention, with more testing occurring during weeks 12, 24, 36, and 52 than the other testing periods.

At testing period visits participants will be asked to complete some or all of the following: body weight measurement; blood sampling; 24-hour urine collection; stool sample collection; DXA scan; peripheral quantitative computed tomography (pQCT) scan; completion of health, physical activity, and nutrition questionnaires; completion of supplement/symptom, diet, and physical activity logs.

A total of 300 participants will be enrolled and screed with an expected randomization of 79 participants per group. The investigators anticipate a 20% drop-out rate between baseline and week 52, thus will anticipate having a final sample size of 63 participants per group complete the study. This sample size provides over 80% power to detect differences with the primary BMD, bone geometry, and bone strength variables.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 300 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Randomized Control Trial of Dietary Supplementation With Dried Plums on Bone Density, Geometry and Estimated Bone Strength in Postmenopausal Women
Study Start Date : June 2016
Estimated Primary Completion Date : July 2020
Estimated Study Completion Date : July 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Ca2+/VitD Control
Participants will take calcium and vitamin D supplements for the duration of the baseline and intervention. Participants will be asked to refrain from consumption of dried plums for the duration of the intervention (52 weeks).
Dietary Supplement: Calcium supplement
All participants will consume calcium supplements for the duration of baseline and intervention.

Dietary Supplement: Vitamin D supplement
All participants will consume vitamin D supplements for the duration of baseline and intervention.

Experimental: 50g Dried Plums
Participants will take calcium and vitamin D supplements for the duration of the baseline and intervention. Additionally, participants will be provided with dried plums and asked to consume 6 (50g) dried plums per day for the duration of the intervention (52 weeks).
Dietary Supplement: Dried Plum
Participants randomized to the 50g dried plum group will consume 6 dried plums per day for the duration of the 52 week intervention. Participants randomized to the 100g dried plum group will consume 12 dried plums per day for the duration of the 52 week intervention.
Other Name: Prunes

Dietary Supplement: Calcium supplement
All participants will consume calcium supplements for the duration of baseline and intervention.

Dietary Supplement: Vitamin D supplement
All participants will consume vitamin D supplements for the duration of baseline and intervention.

Experimental: 100g Dried Plums
Participants will take calcium and vitamin D supplements for the duration of the baseline and intervention. Additionally, participants will be provided with dried plums and asked to consume 12 (100g) dried plums per day for the duration of the intervention (52 weeks).
Dietary Supplement: Dried Plum
Participants randomized to the 50g dried plum group will consume 6 dried plums per day for the duration of the 52 week intervention. Participants randomized to the 100g dried plum group will consume 12 dried plums per day for the duration of the 52 week intervention.
Other Name: Prunes

Dietary Supplement: Calcium supplement
All participants will consume calcium supplements for the duration of baseline and intervention.

Dietary Supplement: Vitamin D supplement
All participants will consume vitamin D supplements for the duration of baseline and intervention.




Primary Outcome Measures :
  1. Percent change from baseline in areal bone mineral density (via DXA) of the lumbar spine, total hip, and femoral neck [ Time Frame: at screening, week 24, and week 52 ]
    Percent change in areal BMD measured during screening, and weeks 24 and 52 of the 52 week dietary intervention at the lumbar spine, total hip, and femoral neck.


Secondary Outcome Measures :
  1. Percent change from baseline in DXA hip structural analysis [ Time Frame: at screening, week 24, and week 52 ]
    Percent change in hip structural analysis (HSA) measured during screening, and weeks 24 and 52 of the 52 week dietary intervention at the total hip.

  2. Percent change from baseline in DXA spine trabecular bone score [ Time Frame: at screening, week 24, and week 52 ]
    Percent change in trabecular bone score (TBS) measured during screening, and weeks 24 and 52 of the 52 week dietary intervention at the lumbar spine.

  3. Percent change from baseline in pQCT volumetric BMD of the tibia and radius [ Time Frame: at baseline, week 24, and week 52 ]
    Percent change in volumetric BMD, cortical and trabecular compartments, measured during baseline, and weeks 24 and 52 of the 52 week dietary intervention at the tibia and radius. The combination of measurements will provide an overall picture of the 3-dimensional structure of a weight bearing (tibia) and non-weight bearing (radius) site and how the sites are impacted by the intervention.

  4. Percent change from baseline in pQCT geometry measurements of the tibia and radius [ Time Frame: at baseline, week 24, and week 52 ]
    Percent change in bone geometry estimates measured during baseline, and weeks 24 and 52 of the 52 week dietary intervention at the tibia and radius. The combination of measurements will provide an overall picture of the 3-dimensional structure of a weight bearing (tibia) and non-weight bearing (radius) site and how the sites are impacted by the intervention.

  5. Percent change from baseline in pQCT strength measurements of the tibia and radius [ Time Frame: at baseline, week 24, and week 52 ]
    Percent change in bone strength estimates measured during baseline, and weeks 24 and 52 of the 52 week dietary intervention at the tibia and radius. The combination of measurements will provide an overall picture of the 3-dimensional structure of a weight bearing (tibia) and non-weight bearing (radius) site and how the sites are impacted by the intervention.

  6. Change from baseline in bone turnover markers [ Time Frame: at baseline, week 12, week 24, week 36, and week 52 ]
    Change in serially-sampled fasting serum concentrations of bone formation (N-terminal type 1 procollagen; P1NP) and bone resorption (crosslaps; CTx) before, during and after the dietary intervention. The combined measures will provide information regarding changes in the rate of bone resorption and bone formation.


Other Outcome Measures:
  1. Change from baseline in cellular bone metabolism [ Time Frame: at baseline, week 12, week 24, week 36, and week 52 ]
    Change in serially-sampled fasting serum concentrations of bone signaling markers (i.e., Insulin like growth factor-1 [IGF-1], osteoprotegerin [OPG], receptor activator of nuclear factor kappaB ligand [RANKL], and sclerostin [SOST]) before, during and after the dietary intervention. Changes in these variables will assist in understanding the underlying mechanisms behind changes in the rates of bone resorption and bone formation.

  2. Change from baseline in urine phenolic concentrations [ Time Frame: at baseline and every 4 weeks during the intervention ]
    Change in serially-sampled 24 hour urine concentrations of phenolic compounds attributable to dried plum consumption.

  3. Change from baseline in serum phenolic concentrations [ Time Frame: at baseline, week 12, week 24, week 36, and week 52 ]
    Change in serially-sampled fasting serum concentrations of phenolic compounds attributable to dried plum consumption.

  4. Change from baseline in expression of inflammatory markers [ Time Frame: at baseline, week 12, week 24, week 36, and week 52 ]
    Change in peripheral blood mononuclear cell (PBMC) gene expression of inflammatory markers before, during and after the dietary intervention. Additionally, the relationship between the changes in gene expression of inflammation markers and bone outcomes will be explored. The combined changes of the gene expression of inflammatory markers will provide a comprehensive picture of the inflammatory environment of the participants before, during and following the dietary intervention. This comprehensive picture will assist in understanding the mechanisms by which the inflammatory environment contributes to bone loss in postmenopausal women and how the dietary intervention impacts these factors.

  5. Change from baseline in gut microbiome [ Time Frame: at baseline, week 24, and week 52 ]
    Serially-sampled stool samples for assessment of changes in the gut microbiome before, during and after the dietary intervention. Additionally, the relationship between the changes in the gut microbiome and bone outcomes will be explored.



Information from the National Library of Medicine

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Ages Eligible for Study:   55 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Postmenopausal women
  • not severely obese (BMI < 40 kg/m2);
  • healthy (determined by a screening questionnaire, complete metabolic panel);
  • willing to include dried plums in their daily diet;
  • not taking any natural dietary supplement containing phenolics, blueberries or apples for at least 2 months prior to study entry; can stop for 2 months to meet entry criteria
  • non-smoking; ambulatory;
  • low BMD as measured by dual energy X-ray absorptiometry (DXA). Eligible BMD values (T-scores) for DXA measures of the lumbar spine, total hip and/or femoral neck will correspond to T-scores between 0 and -3.0.

Exclusion Criteria:

  • Women who regularly consume dried plums, dried apples, prune juice, or heavy consumers of blueberries (1 cup or more/day). Potential volunteers who will refrain from consumption of the afore mentioned foods for the duration of the study will become eligible after a 2 month washout period;
  • vitamin D deficiency (<20 ng/mL);
  • history of vertebral fracture or fragility fracture of the wrist, humerus, hip or pelvis after age 50 yr);
  • untreated hyper- or hypothyroidism;
  • current hyper- or hypoparathyroidism;
  • significantly impaired renal function; high potassium
  • current hypo- or hypercalcemia;
  • history of spinal stenosis;
  • history of heart attack, stroke, thromboembolism, kidney disease, malabsorption syndrome, seizure disorders;
  • positive for HIV, Hep-C or Hep-B surface antigen and malignancy.
  • Use of the following agents affecting bone metabolism:

    • intravenous bisphosphonates at any time;
    • fluoride (for osteoporosis) within the past 24 months;
    • denosumab at any time;
    • bisphosphonates, parathyroid hormone or strontium within the past 12 months;
    • calcitonin or selective estrogen receptor modulators within the past 12 months;
    • systemic oral or transdermal estrogen within the past 3 months;
    • systemic glucocorticosteroids (≥ 5 mg prednisone equivalent per day for more than 10 days); or
    • tibolone within the past 3 months.
  • Participants who will not consume study therapy or will not stop taking natural product supplements of their own selection.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02822378


Contacts
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Contact: Mary Jane De Souza, PhD 814-863-0045 mjd34@psu.edu

Locations
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United States, Pennsylvania
Women's Health and Exercise Laboratories, The Pennsylvania State University Recruiting
University Park, Pennsylvania, United States, 16802
Contact: Mary Jane De Souza, PhD    814-863-0045    mjd34@psu.edu   
Sub-Investigator: Nancy I Williams, Sc.D.         
Principal Investigator: Mary Jane De Souza, Ph.D.         
Sponsors and Collaborators
Penn State University
California Dried Plum Board
Investigators
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Principal Investigator: Mary Jane De Souza, PhD The Pennsylvania State University

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Responsible Party: Mary Jane DeSouza, Professor of Kinesiology and Physiology, Penn State University
ClinicalTrials.gov Identifier: NCT02822378     History of Changes
Other Study ID Numbers: Study00004252
First Posted: July 4, 2016    Key Record Dates
Last Update Posted: December 20, 2018
Last Verified: December 2018

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Mary Jane DeSouza, Penn State University:
Postmenopausal Osteoporosis
Human
Female
Non-pharmacologic therapy

Additional relevant MeSH terms:
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Osteoporosis
Osteoporosis, Postmenopausal
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases
Metabolic Diseases
Vitamin D
Ergocalciferols
Calcium, Dietary
Vitamins
Calcium
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs
Bone Density Conservation Agents
Calcium-Regulating Hormones and Agents