ACAROS: Efficacy of Potassium Citrate in the Treatment of Postmenopausal Osteopenia
Sponsor
Istituto Ortopedico Rizzoli (Other)
Overall Status
Completed
CT.gov ID
NCT02731820
Collaborator
(none)
40
1
2
25
1.6
Study Details
Study Description
Brief Summary
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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
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 Design
Study Type:
Interventional
Actual Enrollment
:
40 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose:
Prevention
Official Title:
Efficacy of Potassium Citrate in the Treatment of Postmenopausal Osteopenia. A Randomized, Placebo-controlled, Double Blind Investigation.
Actual Study Start Date
:
Sep 1, 2015
Actual Primary Completion Date
:
Aug 30, 2017
Actual Study Completion Date
:
Sep 30, 2017
Arms and Interventions
| 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:
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: Placebo
Excipients: 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:
Dietary Supplement: Calcium carbonate
500 mg/die calcium carbonate daily by mouth
|
Outcome Measures
Primary Outcome Measures
- Changes in Serum Level of Carboxyterminal Cross-linked Telopeptide of Type I Collagen (CTX); Over Time, i.e. Baseline, 3 Months, 6 Months. [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.
- Changes in Serum Levels of "Tartrate-resistant Acid Phosphatase 5b Isoenzyme" (TRAcP5b) Over Time, i.e. Baseline, 3 Months, 6 Months. [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.
- Changes in Serum Levels of "N-terminal Propeptide of Type I Procollagen" (P1NP) Over Time, i.e. Baseline, 3 Months, 6 Months. [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.
- Changes in Serum Levels of "Bone-specific Alkaline Phosphatase" (BAP) Over Time, i.e. Baseline, 3 Months, 6 Months. [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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
N/A
and Older
Sexes Eligible for Study:
Female
Accepts Healthy Volunteers:
No
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Istituto Ortopedico Rizzoli | Bologna | Italy | 40136 |
Sponsors and Collaborators
- Istituto Ortopedico Rizzoli
Investigators
- Principal Investigator: Nicola Baldini, MD, Prof., Istituto Ortopedico Rizzoli
Study Documents (Full-Text)
More Information
Additional Information:
Publications
- Arnett TR. Acidosis, hypoxia and bone. Arch Biochem Biophys. 2010 Nov 1;503(1):103-9. doi: 10.1016/j.abb.2010.07.021. Epub 2010 Jul 23. Review.
- Hanley DA, Whiting SJ. Does a high dietary acid content cause bone loss, and can bone loss be prevented with an alkaline diet? J Clin Densitom. 2013 Oct-Dec;16(4):420-5. doi: 10.1016/j.jocd.2013.08.014. Epub 2013 Oct 2. Review.
- Jehle S, Hulter HN, Krapf R. Effect of potassium citrate on bone density, microarchitecture, and fracture risk in healthy older adults without osteoporosis: a randomized controlled trial. J Clin Endocrinol Metab. 2013 Jan;98(1):207-17. doi: 10.1210/jc.2012-3099. Epub 2012 Nov 15.
- Lambert H, Frassetto L, Moore JB, Torgerson D, Gannon R, Burckhardt P, Lanham-New S. The effect of supplementation with alkaline potassium salts on bone metabolism: a meta-analysis. Osteoporos Int. 2015 Apr;26(4):1311-8. doi: 10.1007/s00198-014-3006-9. Epub 2015 Jan 9.
Responsible Party:
Nicola Baldini,
MD, Professor,
Istituto Ortopedico Rizzoli
ClinicalTrials.gov Identifier:
NCT02731820
Other Study ID Numbers:
- 6013_IOR
- 1676
First Posted:
Apr 8, 2016
Last Update Posted:
Nov 12, 2019
Last Verified:
Oct 1, 2019
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Keywords provided by Nicola Baldini,
MD, Professor,
Istituto Ortopedico Rizzoli
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Participants were recruited among the cohort of post-menopausal women attending to the Radiodiagnostic Unit of Istituto Ortopedico Rizzoli (IOR) from September 2015 to February 2017 to perform the periodic measurements of lumbar (at L2-L4 level) and femoral bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA). |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Treatment Group, Potassium Citrate | Control Group, Placebo |
|---|---|---|
| Arm/Group Description | Potassium citrate Calcium carbonate Vitamin D3 Potassium citrate: Kcitr 3.064 milligrams daily in two tablets by mouth (1.032 milligrams every 12 hours) Vitamin D3: 400 IU/die Vitamin D3 daily by mouth Calcium carbonate: 500 mg/die calcium carbonate daily by mouth | Placebo (Excipients) Calcium carbonate Vitamin D3 Placebo: Excipients: 3.064 milligrams daily in two tablets by mouth (1.032 milligrams every 12 hours) Vitamin D3: 400 IU/die Vitamin D3 daily by mouth Calcium carbonate: 500 mg/die calcium carbonate daily by mouth |
| Period Title: Overall Study | ||
| STARTED | 20 | 20 |
| COMPLETED | 17 | 18 |
| NOT COMPLETED | 3 | 2 |
Baseline Characteristics
| Arm/Group Title | Treatment Group, Potassium Citrate | Control Group, Placebo | Total |
|---|---|---|---|
| Arm/Group Description | Potassium citrate Calcium carbonate Vitamin D3 Potassium citrate: Kcitr 3.064 milligrams daily in two tablets by mouth (1.032 milligrams every 12 hours) Vitamin D3: 400 IU/die Vitamin D3 daily by mouth Calcium carbonate: 500 mg/die calcium carbonate daily by mouth | Placebo (Excipients) Calcium carbonate Vitamin D3 Placebo: Excipients: 3.064 milligrams daily in two tablets by mouth (1.032 milligrams every 12 hours) Vitamin D3: 400 IU/die Vitamin D3 daily by mouth Calcium carbonate: 500 mg/die calcium carbonate daily by mouth | Total of all reporting groups |
| Overall Participants | 20 | 20 | 40 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
60.8
(4.67)
|
58.2
(4.95)
|
59.5
(4.93)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
20
100%
|
20
100%
|
40
100%
|
| Male |
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
0
0%
|
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
0
0%
|
0
0%
|
| White |
20
100%
|
20
100%
|
40
100%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Race/Ethnicity, Customized (Count of Participants) | |||
| Caucasian |
20
100%
|
20
100%
|
40
100%
|
| Region of Enrollment (participants) [Number] | |||
| Italy |
20
100%
|
20
100%
|
40
100%
|
| Body mass index (BMI) (kg/m^2) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [kg/m^2] |
23.6
(4.4)
|
22.9
(3.8)
|
23.3
(4.1)
|
| T score (BMD femural neck) (scores on a scale) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [scores on a scale] |
-1.6
(0.4)
|
-1.7
(0.5)
|
-1.6
(0.5)
|
| T score (L2 - L4) (scores on a scale) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [scores on a scale] |
-1.7
(0.5)
|
-1.4
(0.6)
|
-1.6
(0.6)
|
| Major osteoporotic risk (% (percentage probability)) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [% (percentage probability)] |
5.7
(3.4)
|
4.8
(1.5)
|
5.2
(2.6)
|
| Minor osteoporotic risk (% (percentage probability)) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [% (percentage probability)] |
1.1
(0.8)
|
1.0
(0.5)
|
1.0
(0.6)
|
| pH (24h urine) (pH value) [Mean (Full Range) ] | |||
| Mean (Full Range) [pH value] |
6.13
|
6.03
|
6.08
|
| pH (fasting-morning urine) (pH value) [Mean (Full Range) ] | |||
| Mean (Full Range) [pH value] |
6.13
|
5.87
|
6.00
|
| Potassium (24h urine) (milliequivalent day-1) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [milliequivalent day-1] |
28.60
(14.97)
|
30.40
(12.98)
|
29.50
(13.85)
|
| Citrate (24h urine) (mmol day-1) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [mmol day-1] |
2.97
(1.68)
|
3.50
(1.74)
|
3.24
(1.71)
|
| Citrate (fasting-morning urine) (mol mol-1) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [mol mol-1] |
2.77
(1.39)
|
3.40
(2.39)
|
3.09
(1.96)
|
Outcome Measures
| Title | Changes in Serum Level of Carboxyterminal Cross-linked Telopeptide of Type I Collagen (CTX); Over Time, i.e. Baseline, 3 Months, 6 Months. |
|---|---|
| Description | 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. |
| Time Frame | Baseline (T0), 3 months (T3) 6 months (T6) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 3/20 patients in the Treatment group did not complete the follow up (n= 1 re-evaluation of the inclusion criteria; n=1 gastritis; n=1 total hip arthroplasty). 2/20 patients in the Placebo group did not complete the follow up (n=2 persistent constipation) |
| Arm/Group Title | Treatment Group, Potassium Citrate | Control Group, Placebo |
|---|---|---|
| Arm/Group Description | Potassium citrate Calcium carbonate Vitamin D3 Potassium citrate: Kcitr 3.064 milligrams daily in two tablets by mouth (1.032 milligrams every 12 hours) Vitamin D3: 400 IU/die Vitamin D3 daily by mouth Calcium carbonate: 500 mg/die calcium carbonate daily by mouth | Placebo (Excipients) Calcium carbonate Vitamin D3 Placebo: Excipients: 3.064 milligrams daily in two tablets by mouth (1.032 milligrams every 12 hours) Vitamin D3: 400 IU/die Vitamin D3 daily by mouth Calcium carbonate: 500 mg/die calcium carbonate daily by mouth |
| Measure Participants | 20 | 20 |
| Baseline (T0) |
0.64
(0.08)
|
0.64
(0.05)
|
| 3 months (T3) |
0.63
(0.08)
|
0.56
(0.05)
|
| 6 months (T6) |
0.53
(0.08)
|
0.54
(0.06)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Treatment Group, Potassium Citrate |
|---|---|---|
| Comments | Paired analysis within the group to evaluate the effect of Potassium Citrate: T3 vs T0 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.172 |
| Comments | ||
| Method | t-test, 1 sided | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Treatment Group, Potassium Citrate |
|---|---|---|
| Comments | Paired analysis within the group to evaluate the effect of Potassium Citrate: T6 vs T0 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.027 |
| Comments | ||
| Method | t-test, 1 sided | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Treatment Group, Potassium Citrate |
|---|---|---|
| Comments | Paired analysis within the group to evaluate the effect of Potassium Citrate: T6 vs T3 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.053 |
| Comments | ||
| Method | t-test, 1 sided | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Control Group, Placebo |
|---|---|---|
| Comments | Paired analysis within the group to evaluate the effect of Placebo: T3 vs T0 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.002 |
| Comments | ||
| Method | t-test, 1 sided | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Control Group, Placebo |
|---|---|---|
| Comments | Paired analysis within the group to evaluate the effect of Placebo: T6 vs T0 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.006 |
| Comments | ||
| Method | t-test, 1 sided | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Control Group, Placebo |
|---|---|---|
| Comments | Paired analysis within the group to evaluate the effect of Placebo: T6 vs T3 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.139 |
| Comments | ||
| Method | t-test, 1 sided | |
| Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Treatment Group, Potassium Citrate, Control Group, Placebo |
|---|---|---|
| Comments | Independent comparison (unpaired analysis) between Potassium Citrate and Placebo at T0 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.967 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Treatment Group, Potassium Citrate, Control Group, Placebo |
|---|---|---|
| Comments | Independent comparison (unpaired analysis) between Potassium Citrate and Placebo at T3 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.446 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Treatment Group, Potassium Citrate, Control Group, Placebo |
|---|---|---|
| Comments | Independent comparison (unpaired analysis) between Potassium Citrate and Placebo at T6 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.869 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
| Title | Changes in Serum Levels of "Tartrate-resistant Acid Phosphatase 5b Isoenzyme" (TRAcP5b) Over Time, i.e. Baseline, 3 Months, 6 Months. |
|---|---|
| Description | 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. |
| Time Frame | Baseline (T0), 3 months (T3) 6 months (T6) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 3/20 patients in the Treatment group did not complete the follow up (n= 1 re-evaluation of the inclusion criteria; n=1 gastritis; n=1 total hip arthroplasty). 2/20 patients in the Placebo group did not complete the follow up (n=2 persistent constipation) |
| Arm/Group Title | Treatment Group, Potassium Citrate | Control Group, Placebo |
|---|---|---|
| Arm/Group Description | Potassium citrate Calcium carbonate Vitamin D3 Potassium citrate: Kcitr 3.064 milligrams daily in two tablets by mouth (1.032 milligrams every 12 hours) Vitamin D3: 400 IU/die Vitamin D3 daily by mouth Calcium carbonate: 500 mg/die calcium carbonate daily by mouth | Placebo (Excipients) Calcium carbonate Vitamin D3 Placebo: Excipients: 3.064 milligrams daily in two tablets by mouth (1.032 milligrams every 12 hours) Vitamin D3: 400 IU/die Vitamin D3 daily by mouth Calcium carbonate: 500 mg/die calcium carbonate daily by mouth |
| Measure Participants | 20 | 20 |
| Baseline (T0) |
2.35
(0.20)
|
2.64
(0.22)
|
| 3 months (T3) |
2.79
(0.27)
|
2.85
(0.22)
|
| 6 months (T6) |
2.69
(0.29)
|
2.25
(0.14)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Treatment Group, Potassium Citrate |
|---|---|---|
| Comments | Paired analysis within the group to evaluate the effect of Potassium Citrate: T3 vs T0 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.954 |
| Comments | ||
| Method | t-test, 1 sided | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Treatment Group, Potassium Citrate |
|---|---|---|
| Comments | Paired analysis within the group to evaluate the effect of Potassium Citrate: T6 vs T0 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.798 |
| Comments | ||
| Method | t-test, 1 sided | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Treatment Group, Potassium Citrate |
|---|---|---|
| Comments | Paired analysis within the group to evaluate the effect of Potassium Citrate: T6 vs T3 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.377 |
| Comments | ||
| Method | t-test, 1 sided | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Control Group, Placebo |
|---|---|---|
| Comments | Paired analysis within the group to evaluate the effect of Placebo: T3 vs T0 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.886 |
| Comments | ||
| Method | t-test, 1 sided | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Control Group, Placebo |
|---|---|---|
| Comments | Paired analysis within the group to evaluate the effect of Placebo: T6 vs T0 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.040 |
| Comments | ||
| Method | t-test, 1 sided | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Control Group, Placebo |
|---|---|---|
| Comments | Paired analysis within the group to evaluate the effect of Placebo: T6 vs T3 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.017 |
| Comments | ||
| Method | t-test, 1 sided | |
| Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Treatment Group, Potassium Citrate, Control Group, Placebo |
|---|---|---|
| Comments | Independent comparison (unpaired analysis) between Potassium Citrate and Placebo at T0 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.343 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Treatment Group, Potassium Citrate, Control Group, Placebo |
|---|---|---|
| Comments | Independent comparison (unpaired analysis) between Potassium Citrate and Placebo at T3 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.859 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Treatment Group, Potassium Citrate, Control Group, Placebo |
|---|---|---|
| Comments | Independent comparison (unpaired analysis) between Potassium Citrate and Placebo at T6 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.172 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
| Title | Changes in Serum Levels of "N-terminal Propeptide of Type I Procollagen" (P1NP) Over Time, i.e. Baseline, 3 Months, 6 Months. |
|---|---|
| Description | 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. |
| Time Frame | Baseline (T0), 3 months (T3) 6 months (T6) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 3/20 patients in the Treatment group did not complete the follow up (n= 1 re-evaluation of the inclusion criteria; n=1 gastritis; n=1 total hip arthroplasty). 2/20 patients in the Placebo group did not complete the follow up (n=2 persistent constipation) |
| Arm/Group Title | Treatment Group, Potassium Citrate | Control Group, Placebo |
|---|---|---|
| Arm/Group Description | Potassium citrate Calcium carbonate Vitamin D3 Potassium citrate: Kcitr 3.064 milligrams daily in two tablets by mouth (1.032 milligrams every 12 hours) Vitamin D3: 400 IU/die Vitamin D3 daily by mouth Calcium carbonate: 500 mg/die calcium carbonate daily by mouth | Placebo (Excipients) Calcium carbonate Vitamin D3 Placebo: Excipients: 3.064 milligrams daily in two tablets by mouth (1.032 milligrams every 12 hours) Vitamin D3: 400 IU/die Vitamin D3 daily by mouth Calcium carbonate: 500 mg/die calcium carbonate daily by mouth |
| Measure Participants | 20 | 20 |
| Baseline (T0) |
17.45
(1.48)
|
18.82
(1.73)
|
| 3 months (T3) |
16.24
(1.60)
|
18.39
(1.75)
|
| 6 months (T6) |
14.97
(1.51)
|
16.77
(1.89)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Treatment Group, Potassium Citrate |
|---|---|---|
| Comments | Paired analysis within the group to evaluate the effect of Potassium Citrate: T3 vs T0 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.213 |
| Comments | ||
| Method | t-test, 1 sided | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Treatment Group, Potassium Citrate |
|---|---|---|
| Comments | Paired analysis within the group to evaluate the effect of Potassium Citrate: T6 vs T0 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.191 |
| Comments | ||
| Method | t-test, 1 sided | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Treatment Group, Potassium Citrate |
|---|---|---|
| Comments | Paired analysis within the group to evaluate the effect of Potassium Citrate: T6 vs T3 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.234 |
| Comments | ||
| Method | t-test, 1 sided | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Control Group, Placebo |
|---|---|---|
| Comments | Paired analysis within the group to evaluate the effect of Placebo: T3 vs T0 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.370 |
| Comments | ||
| Method | t-test, 1 sided | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Control Group, Placebo |
|---|---|---|
| Comments | Paired analysis within the group to evaluate the effect of Placebo: T6 vs T0 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.176 |
| Comments | ||
| Method | t-test, 1 sided | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Control Group, Placebo |
|---|---|---|
| Comments | Paired analysis within the group to evaluate the effect of Placebo: T6 vs T3 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.139 |
| Comments | ||
| Method | t-test, 1 sided | |
| Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Treatment Group, Potassium Citrate, Control Group, Placebo |
|---|---|---|
| Comments | Independent comparison (unpaired analysis) between Potassium Citrate and Placebo at T0 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.551 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Treatment Group, Potassium Citrate, Control Group, Placebo |
|---|---|---|
| Comments | Independent comparison (unpaired analysis) between Potassium Citrate and Placebo at T3 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.371 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Treatment Group, Potassium Citrate, Control Group, Placebo |
|---|---|---|
| Comments | Independent comparison (unpaired analysis) between Potassium Citrate and Placebo at T6 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.466 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
| Title | Changes in Serum Levels of "Bone-specific Alkaline Phosphatase" (BAP) Over Time, i.e. Baseline, 3 Months, 6 Months. |
|---|---|
| Description | 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. |
| Time Frame | Baseline (T0), 3 months (T3) 6 months (T6) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 3/20 patients in the Treatment group did not complete the follow up (n= 1 re-evaluation of the inclusion criteria; n=1 gastritis; n=1 total hip arthroplasty). 2/20 patients in the Placebo group did not complete the follow up (n=2 persistent constipation) |
| Arm/Group Title | Treatment Group, Potassium Citrate | Control Group, Placebo |
|---|---|---|
| Arm/Group Description | Potassium citrate Calcium carbonate Vitamin D3 Potassium citrate: Kcitr 3.064 milligrams daily in two tablets by mouth (1.032 milligrams every 12 hours) Vitamin D3: 400 IU/die Vitamin D3 daily by mouth Calcium carbonate: 500 mg/die calcium carbonate daily by mouth | Placebo (Excipients) Calcium carbonate Vitamin D3 Placebo: Excipients: 3.064 milligrams daily in two tablets by mouth (1.032 milligrams every 12 hours) Vitamin D3: 400 IU/die Vitamin D3 daily by mouth Calcium carbonate: 500 mg/die calcium carbonate daily by mouth |
| Measure Participants | 20 | 20 |
| Baseline (T0) |
21.89
(1.67)
|
20.36
(1.17)
|
| 3 months (T3) |
19.81
(1.67)
|
18.27
(1.00)
|
| 6 months (T6) |
16.83
(1.37)
|
15.79
(1.09)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Treatment Group, Potassium Citrate |
|---|---|---|
| Comments | Paired analysis within the group to evaluate the effect of Potassium Citrate: T3 vs T0 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.094 |
| Comments | ||
| Method | t-test, 1 sided | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Treatment Group, Potassium Citrate |
|---|---|---|
| Comments | Paired analysis within the group to evaluate the effect of Potassium Citrate: T6 vs T0 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0004 |
| Comments | ||
| Method | t-test, 1 sided | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Treatment Group, Potassium Citrate |
|---|---|---|
| Comments | Paired analysis within the group to evaluate the effect of Potassium Citrate: T6 vs T3 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.008 |
| Comments | ||
| Method | t-test, 1 sided | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Control Group, Placebo |
|---|---|---|
| Comments | Paired analysis within the group to evaluate the effect of Placebo: T3 vs T0 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.002 |
| Comments | ||
| Method | t-test, 1 sided | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Control Group, Placebo |
|---|---|---|
| Comments | Paired analysis within the group to evaluate the effect of Potassium Citrate: T6 vs T0 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | t-test, 1 sided | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Control Group, Placebo |
|---|---|---|
| Comments | Paired analysis within the group to evaluate the effect of Potassium Citrate: T6 vs T3 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0007 |
| Comments | ||
| Method | t-test, 1 sided | |
| Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Treatment Group, Potassium Citrate, Control Group, Placebo |
|---|---|---|
| Comments | Independent comparison (unpaired analysis) between Potassium Citrate and Placebo at T0 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.458 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Treatment Group, Potassium Citrate, Control Group, Placebo |
|---|---|---|
| Comments | Independent comparison (unpaired analysis) between Potassium Citrate and Placebo at T3 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.434 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | Treatment Group, Potassium Citrate, Control Group, Placebo |
|---|---|---|
| Comments | Independent comparison (unpaired analysis) between Potassium Citrate and Placebo at T6 | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.555 |
| Comments | ||
| Method | t-test, 2 sided | |
| Comments | ||
Adverse Events
| Time Frame | Adverse events were recorded at 3 months and 6 months | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | Gastrointestinal disorders | |||
| Arm/Group Title | Treatment Group | Control Group, Placebo | ||
| Arm/Group Description | Potassium citrate Calcium carbonate Vitamin D3 Potassium citrate: Kcitr 3.064 milligrams daily in two tablets by mouth (1.032 milligrams every 12 hours) Vitamin D3: 400 IU/die Vitamin D3 daily by mouth Calcium carbonate: 500 mg/die calcium carbonate daily by mouth | Placebo (Excipients) Calcium carbonate Vitamin D3 Placebo: Excipients: 3.064 milligrams daily in two tablets by mouth (1.032 milligrams every 12 hours) Vitamin D3: 400 IU/die Vitamin D3 daily by mouth Calcium carbonate: 500 mg/die calcium carbonate daily by mouth | ||
All Cause Mortality |
||||
| Treatment Group | Control Group, Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/20 (0%) | 0/20 (0%) | ||
Serious Adverse Events |
||||
| Treatment Group | Control Group, Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/20 (0%) | 0/20 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Treatment Group | Control Group, Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/20 (5%) | 2/20 (10%) | ||
| Gastrointestinal disorders | ||||
| Gastritis | 1/20 (5%) | 1 | 0/20 (0%) | 0 |
| Constipation | 0/20 (0%) | 0 | 2/20 (10%) | 2 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Director of Clinical Trials |
|---|---|
| Organization | Istituto Ortopedico Rizzoli |
| Phone | +39 051.6366392 |
| ctc@ior.it |
Responsible Party:
Nicola Baldini,
MD, Professor,
Istituto Ortopedico Rizzoli
ClinicalTrials.gov Identifier:
NCT02731820
Other Study ID Numbers:
- 6013_IOR
- 1676
First Posted:
Apr 8, 2016
Last Update Posted:
Nov 12, 2019
Last Verified:
Oct 1, 2019