Trial Outcomes & Findings for Efficacy of Potassium Citrate in the Treatment of Postmenopausal Osteopenia (NCT NCT02731820)

Last Updated: 2019-11-12

Results Overview

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.

Recruitment status

COMPLETED

Study phase

Target enrollment

40 participants

Primary outcome timeframe

Baseline (T0), 3 months (T3) 6 months (T6)

Results posted on

2019-11-12

Participant Flow

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).

Participant milestones

Participant milestones
Measure	Treatment Group, Potassium Citrate 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	Control Group, Placebo 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
Overall Study STARTED	20	20
Overall Study COMPLETED	17	18
Overall Study NOT COMPLETED	3	2

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Efficacy of Potassium Citrate in the Treatment of Postmenopausal Osteopenia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment Group, Potassium Citrate n=20 Participants 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	Control Group, Placebo n=20 Participants 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 n=40 Participants Total of all reporting groups
Age, Continuous	60.8 years STANDARD_DEVIATION 4.67 • n=5 Participants	58.2 years STANDARD_DEVIATION 4.95 • n=7 Participants	59.5 years STANDARD_DEVIATION 4.93 • n=5 Participants
Sex: Female, Male Female	20 Participants n=5 Participants	20 Participants n=7 Participants	40 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	20 Participants n=5 Participants	20 Participants n=7 Participants	40 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian	20 Participants n=5 Participants	20 Participants n=7 Participants	40 Participants n=5 Participants
Region of Enrollment Italy	20 participants n=5 Participants	20 participants n=7 Participants	40 participants n=5 Participants
Body mass index (BMI)	23.6 kg/m^2 STANDARD_DEVIATION 4.4 • n=5 Participants	22.9 kg/m^2 STANDARD_DEVIATION 3.8 • n=7 Participants	23.3 kg/m^2 STANDARD_DEVIATION 4.1 • n=5 Participants
T score (BMD femural neck)	-1.6 scores on a scale STANDARD_DEVIATION 0.4 • n=5 Participants	-1.7 scores on a scale STANDARD_DEVIATION 0.5 • n=7 Participants	-1.6 scores on a scale STANDARD_DEVIATION 0.5 • n=5 Participants
T score (L2 - L4)	-1.7 scores on a scale STANDARD_DEVIATION 0.5 • n=5 Participants	-1.4 scores on a scale STANDARD_DEVIATION 0.6 • n=7 Participants	-1.6 scores on a scale STANDARD_DEVIATION 0.6 • n=5 Participants
Major osteoporotic risk	5.7 % (percentage probability) STANDARD_DEVIATION 3.4 • n=5 Participants	4.8 % (percentage probability) STANDARD_DEVIATION 1.5 • n=7 Participants	5.2 % (percentage probability) STANDARD_DEVIATION 2.6 • n=5 Participants
Minor osteoporotic risk	1.1 % (percentage probability) STANDARD_DEVIATION 0.8 • n=5 Participants	1.0 % (percentage probability) STANDARD_DEVIATION 0.5 • n=7 Participants	1.0 % (percentage probability) STANDARD_DEVIATION 0.6 • n=5 Participants
pH (24h urine)	6.13 pH value n=5 Participants	6.03 pH value n=7 Participants	6.08 pH value n=5 Participants
pH (fasting-morning urine)	6.13 pH value n=5 Participants	5.87 pH value n=7 Participants	6.00 pH value n=5 Participants
Potassium (24h urine)	28.60 milliequivalent day-1 STANDARD_DEVIATION 14.97 • n=5 Participants	30.40 milliequivalent day-1 STANDARD_DEVIATION 12.98 • n=7 Participants	29.50 milliequivalent day-1 STANDARD_DEVIATION 13.85 • n=5 Participants
Citrate (24h urine)	2.97 mmol day-1 STANDARD_DEVIATION 1.68 • n=5 Participants	3.50 mmol day-1 STANDARD_DEVIATION 1.74 • n=7 Participants	3.24 mmol day-1 STANDARD_DEVIATION 1.71 • n=5 Participants
Citrate (fasting-morning urine)	2.77 mol mol-1 STANDARD_DEVIATION 1.39 • n=5 Participants	3.40 mol mol-1 STANDARD_DEVIATION 2.39 • n=7 Participants	3.09 mol mol-1 STANDARD_DEVIATION 1.96 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline (T0), 3 months (T3) 6 months (T6)

Population: 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)

Outcome measures

Outcome measures
Measure	Treatment Group, Potassium Citrate n=20 Participants 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	Control Group, Placebo n=20 Participants 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
Changes in Serum Level of Carboxyterminal Cross-linked Telopeptide of Type I Collagen (CTX); Over Time, i.e. Baseline, 3 Months, 6 Months. 6 months (T6)	0.53 µg/L Standard Error 0.08	0.54 µg/L Standard Error 0.06
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)	0.64 µg/L Standard Error 0.08	0.64 µg/L Standard Error 0.05
Changes in Serum Level of Carboxyterminal Cross-linked Telopeptide of Type I Collagen (CTX); Over Time, i.e. Baseline, 3 Months, 6 Months. 3 months (T3)	0.63 µg/L Standard Error 0.08	0.56 µg/L Standard Error 0.05

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Treatment Group, Potassium Citrate n=20 Participants 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	Control Group, Placebo n=20 Participants 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
Changes in Serum Levels of "Tartrate-resistant Acid Phosphatase 5b Isoenzyme" (TRAcP5b) Over Time, i.e. Baseline, 3 Months, 6 Months. Baseline (T0)	2.35 U/L Standard Error 0.20	2.64 U/L Standard Error 0.22
Changes in Serum Levels of "Tartrate-resistant Acid Phosphatase 5b Isoenzyme" (TRAcP5b) Over Time, i.e. Baseline, 3 Months, 6 Months. 3 months (T3)	2.79 U/L Standard Error 0.27	2.85 U/L Standard Error 0.22
Changes in Serum Levels of "Tartrate-resistant Acid Phosphatase 5b Isoenzyme" (TRAcP5b) Over Time, i.e. Baseline, 3 Months, 6 Months. 6 months (T6)	2.69 U/L Standard Error 0.29	2.25 U/L Standard Error 0.14

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Treatment Group, Potassium Citrate n=20 Participants 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	Control Group, Placebo n=20 Participants 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
Changes in Serum Levels of "N-terminal Propeptide of Type I Procollagen" (P1NP) Over Time, i.e. Baseline, 3 Months, 6 Months. Baseline (T0)	17.45 pg/L Standard Error 1.48	18.82 pg/L Standard Error 1.73
Changes in Serum Levels of "N-terminal Propeptide of Type I Procollagen" (P1NP) Over Time, i.e. Baseline, 3 Months, 6 Months. 3 months (T3)	16.24 pg/L Standard Error 1.60	18.39 pg/L Standard Error 1.75
Changes in Serum Levels of "N-terminal Propeptide of Type I Procollagen" (P1NP) Over Time, i.e. Baseline, 3 Months, 6 Months. 6 months (T6)	14.97 pg/L Standard Error 1.51	16.77 pg/L Standard Error 1.89

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Treatment Group, Potassium Citrate n=20 Participants 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	Control Group, Placebo n=20 Participants 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
Changes in Serum Levels of "Bone-specific Alkaline Phosphatase" (BAP) Over Time, i.e. Baseline, 3 Months, 6 Months. Baseline (T0)	21.89 µg/L Standard Error 1.67	20.36 µg/L Standard Error 1.17
Changes in Serum Levels of "Bone-specific Alkaline Phosphatase" (BAP) Over Time, i.e. Baseline, 3 Months, 6 Months. 3 months (T3)	19.81 µg/L Standard Error 1.67	18.27 µg/L Standard Error 1.00
Changes in Serum Levels of "Bone-specific Alkaline Phosphatase" (BAP) Over Time, i.e. Baseline, 3 Months, 6 Months. 6 months (T6)	16.83 µg/L Standard Error 1.37	15.79 µg/L Standard Error 1.09

Adverse Events

Treatment Group

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Control Group, Placebo

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Treatment Group n=20 participants at risk 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	Control Group, Placebo n=20 participants at risk 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
Gastrointestinal disorders Gastritis	5.0% 1/20 • Number of events 1 • Adverse events were recorded at 3 months and 6 months Gastrointestinal disorders	0.00% 0/20 • Adverse events were recorded at 3 months and 6 months Gastrointestinal disorders
Gastrointestinal disorders Constipation	0.00% 0/20 • Adverse events were recorded at 3 months and 6 months Gastrointestinal disorders	10.0% 2/20 • Number of events 2 • Adverse events were recorded at 3 months and 6 months Gastrointestinal disorders

Additional Information

Director of Clinical Trials

Istituto Ortopedico Rizzoli

Phone: +39 051.6366392

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place