Efficacy of Potassium Citrate in the Treatment of Postmenopausal Osteopenia (ACAROS)

October 21, 2019 updated by: Nicola Baldini, Istituto Ortopedico Rizzoli

Efficacy of Potassium Citrate in the Treatment of Postmenopausal Osteopenia. A Randomized, Placebo-controlled, Double Blind Investigation.

The purpose of this study is to investigate whether the use of alkali compounds, i.e. potassium citrate (K3C6H5O7, hereinafter KCitr) is effective in preventing the progression of osteopenia.

A randomized clinical trial (RCT, placebo-controlled, double-blind) has been planned to evaluate the effect of the daily administration of KCitr (3 g/die, K 30 mEq).

The efficacy will be evaluated by comparing the circulating levels of bone turnover markers at the baseline and after the treatment (3, 6 months).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Bone tissue carries out some of the important metabolic functions, including the regulation of acid-base balance. In order to buffer the systemic acidosis, the skeleton acts as a "ion exchange column" modifying the composition of the mineral portion, i.e. the hydroxyapatite. There is a linear correlation between elimination of calcium and acidosis: the higher is the acidosis, the higher will be the loss of calcium from bones. In vitro experiments showed that acidosis also directly influences the cellular component of bone by increasing the osteoclast activity and inhibiting the production of the mineralized matrix by osteoblast. Since the low pH is a risk factor that accelerates the bone loss, the use of alkalizing compounds could prevent the osteopenia or support the conventional therapy of the osteoporosis.

KCitr is an alkaline compound which may be used in metabolic acidosis. Potassium is an alkaline metal that plays a pivotal role in the function of all living cells. Citric acid is a key molecule of the Krebs cycle, and it is abundant in bone where exhibits a stabilizing function. Although clinical data regarding the KCitr effectiveness on calcium metabolism are encouraging, it is still unclear whether the beneficial effects are due exclusively to the buffering function or whether KCitr may affect the bone cells activity. The purpose of this study is to evaluate the effects of KCitr on bone metabolism. We hypothesize that administration of potassium citrate to postmenopausal women with osteopenia will delay (or will prevent) the weakening of bone mass.

Postmenopausal women with osteopenia (T score between -1.0 and -2.5) and no history of fracture will be randomized to assume KCitr ate or placebo, daily for six months. Primary outcomes will be evaluated by measuring markers of bone turnover, which will be measured at baseline (before treatment), in the mid-term (3 months) and at the end (6 months).

Study Type

Interventional

Enrollment (Actual)

40

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Bologna, Italy, 40136
        • Istituto Ortopedico Rizzoli

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Postmenopausal women, more than 5 years post menopause
  • Osteopenia (T-score < -1 and > -2.5)
  • Low risk of fracture (FRAX: < 20 major osteoporotic; < 3 hip fracture)

Exclusion Criteria:

  • Hyperkalemia
  • Renal insufficiency
  • Nephrolithiasis
  • Use of potassium sparing diuretics
  • Use of potassium supplements
  • Use of therapies influencing bone metabolism (e.g. corticosteroids, thiazide diuretics, aromatase inhibitors, estrogens)
  • Use of protonic pump inhibitors
  • Current or recent use of bisphosphonates (stopped less than three years prior to the start of the study)
  • Gastrointestinal disorders that hamper nutrient absorption;
  • Mental or psychiatric disorders that preclude the possibility of correctly adhering to the protocol

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment group
Potassium citrate Calcium carbonate Vitamin D3
Dietary supplement: Potassium citrate
Kcitr 3.064 milligrams daily in two tablets by mouth (1.032 milligrams every 12 hours)
Dietary supplement: Vitamin D3
400 IU/die Vitamin D3 daily by mouth
Other Names:
  • Cholecalciferol
Dietary supplement: Calcium carbonate
500 mg/die calcium carbonate daily by mouth
Placebo Comparator: Control group, Placebo
Placebo (Excipients) Calcium carbonate Vitamin D3
Dietary supplement: Vitamin D3
400 IU/die Vitamin D3 daily by mouth
Other Names:
  • Cholecalciferol
Dietary supplement: Calcium carbonate
500 mg/die calcium carbonate daily by mouth
Dietary supplement: Placebo
Excipients: 3.064 milligrams daily in two tablets by mouth (1.032 milligrams every 12 hours)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in Serum Level of Carboxyterminal Cross-linked Telopeptide of Type I Collagen (CTX); Over Time, i.e. Baseline, 3 Months, 6 Months.
Time Frame: Baseline (T0), 3 months (T3) 6 months (T6)

Carboxyterminal cross-linked telopeptide of type I collagen (CTX) is a degradation product of the type I collagen; it is considered as a marker of bone resorption. The concentration of CTX (µg/L) will be measured at T0, T3, and T6 on serum samples (fasting morning samples) using commercially available reagents and following the manufacturer's protocol.

At the end of the study, the results will be aggregated as mean ± standard of the mean, median and min-max range. Data will be statistically analyzed in order to compare the activity of Potassium citrate versus Placebo (unpaired analysis) and to evaluate the effect of Potassium Citrate and Placebo over time (paired analysis).

Differences will be considered to be statistically significant for p-value <0.05.
Baseline (T0), 3 months (T3) 6 months (T6)
Changes in Serum Levels of "Tartrate-resistant Acid Phosphatase 5b Isoenzyme" (TRAcP5b) Over Time, i.e. Baseline, 3 Months, 6 Months.
Time Frame: Baseline (T0), 3 months (T3) 6 months (T6)

Tartrate-resistant acid phosphatase 5b isoenzyme" (TRAcP5b) is a specific product of osteoclasts; it is considered as a marker of bone resorption. The concentration of TRAcP5B (U/L) will be measured at T0, T3, and T6 on serum samples (fasting morning samples) using commercially available reagents and following the manufacturer's protocol. At the end of the study, the results will be aggregated as mean ± standard of the mean, median and min-max range. Data will be statistically analyzed in order to compare the activity of Potassium Citrate versus Placebo (unpaired analysis) and to evaluate the effect of Potassium Citrate and Placebo over time (paired analysis).

Differences will be considered to be statistically significant for p-value <0.05.
Baseline (T0), 3 months (T3) 6 months (T6)
Changes in Serum Levels of "N-terminal Propeptide of Type I Procollagen" (P1NP) Over Time, i.e. Baseline, 3 Months, 6 Months.
Time Frame: Baseline (T0), 3 months (T3) 6 months (T6)

N-terminal propeptide of type I procollagen" (P1NP) is a product of the conversion of procollagen to collagen; it is considered as a marker of bone formation. The concentration of P1NP (pg/L) will be measured at T0, T3, and T6 on serum samples (fasting morning samples) using commercially available reagents and following the manufacturer's protocol. At the end of the study, the results will be aggregated as mean ± standard of the mean, median and min-max range. Data will be statistically analyzed in order to compare the activity of Potassium citrate versus Placebo (unpaired analysis) and to evaluate the effect of Potassium Citrate and Placebo over time (paired analysis).

Differences will be considered to be statistically significant for p-value <0.05.
Baseline (T0), 3 months (T3) 6 months (T6)
Changes in Serum Levels of "Bone-specific Alkaline Phosphatase" (BAP) Over Time, i.e. Baseline, 3 Months, 6 Months.
Time Frame: Baseline (T0), 3 months (T3) 6 months (T6)

Bone-specific alkaline phosphatase (BAP) is a specific product of osteoblasts; it is considered as a marker of bone formation. The concentration of BAP (µg/L) will be measured at T0, T3, and T6 on serum samples (fasting morning samples) using commercially available reagents and following the manufacturer's protocol. At the end of the study, the results will be aggregated as mean ± standard of the mean, median and min-max range. Data will be statistically analyzed in order to compare the activity of Potassium citrate versus Placebo (unpaired analysis) and to evaluate the effect of Potassium Citrate and Placebo over time (paired analysis).

Differences will be considered to be statistically significant for p-value <0.05.
Baseline (T0), 3 months (T3) 6 months (T6)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Istituto Ortopedico Rizzoli

Investigators

  • Principal Investigator: Nicola Baldini, MD, Prof., Istituto Ortopedico Rizzoli

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 1, 2015

Primary Completion (Actual)

August 30, 2017

Study Completion (Actual)

September 30, 2017

Study Registration Dates

First Submitted

March 31, 2016

First Submitted That Met QC Criteria

April 7, 2016

First Posted (Estimate)

April 8, 2016

Study Record Updates

Last Update Posted (Actual)

November 12, 2019

Last Update Submitted That Met QC Criteria

October 21, 2019

Last Verified

October 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 6013_IOR
  • 1676 (Istituto Ortopedico Rizzoli)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

IPD Plan Description

All the results will be available "on request"

Study Data/Documents

  1. Study Protocol
    Information comments: Study protocol is available on request
  2. Clinical Study Report
    Information identifier: doi: 10.3390/nu10091293

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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