Clinical trial NCT04431960: Blackcurrants Modify Gut Microbiota and Reduce Osteoporosis and CVD Risk
Official title: Blackcurrant Modifies Gut Microbiota and Reduces the Risk of Postmenopausal Osteoporosis and Cardiovascular Disease: A Pilot Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Postmenopausal Osteoporosis
Gut Microbiota
Cardiovascular Diseases
Keywords: blackcurrant
gut microbiome
osteoporosis
menopause
bone aging
women
cardiovascular disease
Lead sponsor: University of Connecticut
Sponsor class: OTHER
First posted: 2020-06-16
Enrollment: 51
Sex: FEMALE
Minimum age (years): 45
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The study participants will be randomly assigned to three groups and asked to consume 1 tablet containing 392 mg blackcurrant (BC) extract per capsule (low-BC Group), 2 capsules containing 392 mg BC extract per tablet (total 784 mg/day; high-BC Group), or 1 placebo capsule (Control Group) daily with breakfast meals for 6 months.

To avoid bone deterioration related to calcium and vitamin D deficiency, all participants will take a calcium citrate caplet daily that includes 400 mg calcium and 500 IU vitamin D (Bayer AG, Germany) beginning 2 weeks before the study and lasting for the duration of the study.
Primary purpose: PREVENTION

Brief summary: Aim to evaluate the effects of blackcurrant supplementation on changes in gut microbiome, bone mass, and CVD risk factors in adult women.

Detailed description: Postmenopausal bone loss is a primary contributor to osteoporosis and osteoporotic fractures in adult women in menopause transition. By following women over this period, studies have documented distinct patterns of a decrease in estrogen, a natural antioxidant, simultaneously with adverse alterations in body fat distribution, lipids and lipoproteins, and measures of vascular health, which can increase a woman's risk of developing CVD. Overall goal of this project is to evaluate the effects of blackcurrant (BC) supplementation on changes in gut microbiome, bone mass, and CVD risk factors in adult women. For this purpose, the investigators will conduct a pilot randomized placebo-controlled clinical trial with BC supplementation for 6 months in peri- and early postmenopausal women aged 45-60 years.

The primary endpoint will be whole-body bone mineral density (BMD); secondary endpoints will be gut microbiota composition. To delineate the underlying mechanisms of the action, changes in biomarkers for bone metabolism, bone-related immune and endocrine systemic biomarkers, and CVD risk factors by BC supplementation will be measured in plasma and peripheral blood derived mononuclear cells.

The specific objectives of the study are to investigate the effects of BC extract on: 1) bone mass and bone remodeling markers; 2) changes in the gut microbiota abundance and composition, immune and endocrine biomarkers, and CVD risk factors and their relationships with changes in bone mass.

The proposed study will provide novel insight into whether and how BC consumption reduces the risk of postmenopausal bone loss and CVD in adult women and will improve understanding of the clinical roles of gut microbiome in postmenopausal bone loss. Findings from this study will help increase awareness of the bone and heart health promoting effect of BC and motivate increased production of BC and other berry products in response to the increasing consumer demand.

Eligibility criteria: Inclusion Criteria:

* perimenopausal or early postmenopausal women aged 45-60 years old
* not on HRT for at least one year before the initiation of the study
* maintaining normal exercise level (\<7 h/wk) and willing to avoid exercise 24-h prior to blood and stool sampling and 12-h prior to bone measurements
* willing to ingest a dietary BC supplement or placebo (up to 900 mg/day, two 450 mg capsules) as well as 400 mg calcium and 500 IU vitamin D daily
* willing to avoid other dietary supplements for the duration of the study
* willing to avoid intake of foods extremely rich in anthocyanins and fermented dairy products containing viable Bifidobacteria or Lactobacilli
* willing to have 3 blood draws, 2 stool collections, and 2 bone scans
* willing to take urine pregnancy test if they are perimenopausal.

Exclusion Criteria:

* those with metabolic bone disease, renal disease, cancer, cardiovascular disease, diabetes mellitus, respiratory disease, gastrointestinal disease, liver disease or other chronic diseases
* those with hypertension or on drugs that lower blood pressure
* those with planned surgery during the study period or within 2 weeks of ending the intervention
* taking medications that alter bleeding (such as antiplatelets or anticoagulants) or those with a bleeding disorder
* taking a phenothiazine drug (most commonly used for nausea or mental health conditions)
* having a sensitivity or allergy to any of ingredients for the placebo (rice powder) and calcium/D supplement (calcium citrate, polyethylene glycol, croscarmellose sodium, hydroxypropyl methylcellulose, magnesium stearate, oligofructose enriched inulin, propylene glycol dicaprylate/dicaprate, talc, titanium dioxide, vitamin D3)
* heavy smokers (\>20 cigarettes/day)
* perimenopausal women with any chance or plan of pregnancy
* taking prescription medications known to alter bone and Ca metabolism such as calcitonin, bisphosphonates, raloxifene within 3 months before the start of the study
* taking anabolic agents such as parathyroid hormone, growth hormone, or steroids within 3 months before the start of the study
* planning any procedure that includes iodine, barium or nuclear medicine isotopes in next 7 months
* alcohol consumption exceeding 2 drinks/day (approximately 14 g ethanol per drink) or a total of 12/week
* UConn students and/or employees who any key personnel teach or who report to any key personnel
* study key personnel, spouses of key personnel, or dependents/relatives of any key personnel.

Primary outcomes:
measure: Bone Mineral Density (BMD)
timeFrame: From baseline to 6 months
Secondary outcomes:
measure: Serum Marker of Bone Formation
timeFrame: From baseline to 6 months
measure: Plasma Regulator of Bone Metabolism
timeFrame: From baseline to 6 months
measure: Changes in Plasma Inflammatory Cytokine
timeFrame: From baseline to 6 months
Other outcomes:
measure: Changes in Gut Microbial Composition
timeFrame: from baseline to 6 months
measure: Serum Inflammation Biomarker
timeFrame: from baseline to 6 months
measure: Plasma CVD Risk Factors
timeFrame: from baseline to 6 months
measure: Blood Pressure (SBP/DBP), BMI, WC, Body Composition
timeFrame: from baseline to 6 months
measure: Concentrations of Plasma Immune Markers
timeFrame: from baseline to 6 months
measure: Concentrations of Plasma IGF-1 and cGP
timeFrame: from baseline to 6 months
Locations:
city: Storrs
country: United States
facility: University of Connecticut Department of Nutritional Sciences and Kinesiology Human Performance Laboratory
state: Connecticut
Study officials:
affiliation: University of Connecticut
name: Ock K Chun, PhD
role: PRINCIPAL_INVESTIGATOR
References: