Ignite Creation Date:
2024-05-06 @ 11:04 AM
Last Modification Date:
2024-10-26 @ 12:39 PM
Study NCT ID:
NCT03425747
Status:
COMPLETED
Last Update Posted:
2020-04-03
First Post:
2018-01-27
Brief Title:
Efficacy of Calcium Citrate Versus Calcium Carbonate for the Management of Chronic Hypoparathyroidism
Sponsor:
Campus Bio-Medico University
Organization:
Campus Bio-Medico University
Study Overview
Official Title:
CALCIUM CITRATE vs CALCIUM CARBONATE FOR THE MANAGEMENT OF CHRONIC HYPOPARATHYROIDISM
Status:
COMPLETED
Status Verified Date:
2020-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Hypoparathyroidism is an endocrinopathy characterized by a deficient secretion or action of PTH associated with low calcium level According to the European guideline 2015 standard treatment includes oral calcium salts and active vitamin D metabolites to relieve symptoms of hypocalcaemia maintain serum calcium levels in the low normal range and improve the patients QoL Calcium carbonate is most often used and less expensive than other calcium preparations and contains the highest concentration of elemental calcium per gram 42 It requires gastric hydrochloric acid to form carbonic acid H2CO3 that immediately decomposes into water H2O and carbon dioxide CO2 CO2 is responsible for its side effects such as flatulence constipation and general gastrointestinal disorders Therefore in some patients it is better to find an alternative to calcium carbonate Calcium citrate should be recommended to patients with achlorhydria or on treatment with proton pump inhibitors PPI as well as to patients who preferred to take supplements outside mealtimes furthermore patients with hypoparathyroidism have an increased risk of kidney stones Kidney stones are formed by calcium salts among which the most frequent ones are calcium-oxalate 70-80 followed by calcium-phosphate and uric acid Citrate salts are widely used in the treatmentof nephrolithiasis since have shown an inhibitory effect on kidney stone formation Up to now there are no studies aimed to investigate the efficacy of calcium citrate in the management of subjects with chronic hypoparathyroidism In particular we will investigate if calcium citrate compared to calcium carbonate does not affect the risk of renal stones if it is able to maintain normal calcium levels and if it has an impact on QOL in subjects with chronic hypoparathyroidism
Detailed Description:
BACKGROUND Hypoparathyroidism is an endocrinopathy characterized by a deficient secretion or action of PTH associated with low calcium level It can be primary inadequate PTH activity or secondary peripheral resistance to PTH
The most common cause of chronic Hypoparathyroidism is the postsurgical one it is usually secondary to previous thyroid surgery but may also occur following parathyroidectomy or other cervical surgical procedures Transient Hypoparathyroidism occurs in 30-60 of patients undergoing total or subtotal thyroidectomy About 60-70 of cases of postoperative hypocalcaemia resolve within 4-6 weeks after surgery About 15-25 of patients will develop chronic Hypoparathyroidism The risk of chronic Hypoparathyroidism is closely related to the number of parathyroid glands remaining in situ at operation
Hypocalcemia is defined as serum calcium level albumin adjusted total calcium or ionized calcium below the lower limit of the reference range target range
In literature there are not data that suggest which is the best serum calcium level to maintain during treatment but the aim is to maintain serum calcium level in the lower part or slightly below the lower limit of the reference range adjusted serum calcium level 21-23 or S-Ca2 between 105-115mmolL serum phosphate levels within the reference range serum calcium-phosphate product below 44 mmol2l2 55 mg2dl2 24-hurinary calcium excretion 75 mmol2h 300 mg24h in men 625 mmol24h 250 mg24h in women or 01 mmolkg per 24 h 4 mgkg per 24h in both sexes
In addition to hypocalcemia patients affected by chronic hypoparathyroidism have a higher risk of renal implications such as urolithiasis and renal impairment because lack of PTH reduces calcium absorption and phosphate excretion causing hypercalciuria and hyperphosphatemia
Moreover many patients with hypoparathyroidism complain of reduced quality of life QOL in ways that are difficult to quantify but that are nevertheless of concern Biochemical control with standard therapy is rarely accompanied by improved functioning or sense of well-being Complaints of cognitive dysfunction are common with the term brain fog typically described by patients In support of these issues large cohort studies from Denmark have shown increased risk of hospitalization for depression and affective disorders renal impairment and infections whereas the risk for cancer and overall mortality was not increased
According to the European guideline 2015 standard treatment includes oral calcium salts and active vitamin D metabolites to relieve symptoms of hypocalcaemia maintain serum calcium levels in the low normal range and improve the patients QoL An adequate daily intake of calcium from diet and supplements is advisable Different calcium salts are available as supplements because elemental calcium is highly reactive so it has to be combined with other substances These preparations differ in the concentration of elemental calcium per gram
Calcium carbonate is most often used and less expensive than other calcium preparations and contains the highest concentration of elemental calcium per gram 42 It requires gastric hydrochloric acid to form carbonic acid H2CO3 that immediately decomposes into water H2O and carbon dioxide CO2 CO2 is responsible for its side effects such as flatulence constipation and general gastrointestinal disorders Therefore in some patients it is better to find an alternative to calcium carbonate Calcium citrate for example should be recommended to patients with achlorhydria or on treatment with proton pump inhibitors PPI as well as to patients who preferred to take supplements outside mealtimes
Previous studies showed that calcium citrate in comparison to calcium carbonate causes greater increment in serum calcium concentration and urinary calcium excretion in parallel with greater suppression of serum PTH after Roux-en-Y Gastric bypass and this datum suggests both the pharmacokinetic and pharmacodynamic superiority of calcium citrate
Calcium citrate is also better adsorbed than calcium carbonate after panproctocolectomy so in a condition of a general enteric malabsorption
Up to now there are no studies aimed to investigate the efficacy of calcium citrate in the management of subjects with chronic hypoparathyroidism In particular the investigators will test the efficacy of calcium citrate in maintaining normal calcium level compared to carbonate calcium in subjects with chronic hypoparathyroidism Moreover the investigators will evaluate the impact of calcium citrate on QOL in this kind of patients compared to the gold standard therapy carbonate calcium
MATERIALS AND METHODS Each subject will participate in two phases of the study and each phase will last one month Once every 2 weeks blood and a morning urine sample will be drawn For all the study period participants will be instructed to maintain a predetermined dietary calcium intake 800 mgday with sodium 100 mEqday restrictions All subjects will complete a questionnaire on quality of life at 0 2 4 week during both phases The investigators will use the Rand 36-Item Short Form Health Survey version 10 to evaluate the QOL
Phase 1 According to a block randomization scheme subjects will be assigned to a calcium supplement Drug A or Drug B at the same total amount of elemental calcium that they had taken before the study enrollment The dose of Vitamin D will be equal to the daily dose taken prior to the study and will not be changed during the study period
Phase 2 subjects will be shift to the opposite Drug from drug A to drug B or from drug B to drug A at the same total amount of elemental calcium that they had taken during the last week of the phase 1
SAMPLE SIZE CALCULATION
1 Based on the assumption that the within-patient standard deviation of the calcium oxalate saturation is 05 to demonstrate that calcium citrate does not affect the calcium oxalate saturation a total of 24 patients need to be enrolled in this study This sample size will allow to detect a difference of 043 points at a two-sided 5 significance level with a probability of type II error of 20
2 to demonstrate that calcium citrate is as effective as calcium carbonate in maintaining serum Ca within the acceptable clinical range To this end we will study a sample of 21 people already treated with calcium and vitamin D supplementation Our hypothesis is that at the end of the study period the mean Ca concentration will not be different from the ideal value 9 mgdl accepting a 10 variation as the equivalence limit ie accepting as equivalent values between 81 and 99 mgdl Under these assumptions we would need 11 patients to show equivalence between the two treatments with a alpha error probability of 5 and a beta error probability of 1020 With the available sample size we will be able to establish equivalence with an equivalence limit of 07 ie values between 83 and 97 mgdl
The most common cause of chronic Hypoparathyroidism is the postsurgical one it is usually secondary to previous thyroid surgery but may also occur following parathyroidectomy or other cervical surgical procedures Transient Hypoparathyroidism occurs in 30-60 of patients undergoing total or subtotal thyroidectomy About 60-70 of cases of postoperative hypocalcaemia resolve within 4-6 weeks after surgery About 15-25 of patients will develop chronic Hypoparathyroidism The risk of chronic Hypoparathyroidism is closely related to the number of parathyroid glands remaining in situ at operation
Hypocalcemia is defined as serum calcium level albumin adjusted total calcium or ionized calcium below the lower limit of the reference range target range
In literature there are not data that suggest which is the best serum calcium level to maintain during treatment but the aim is to maintain serum calcium level in the lower part or slightly below the lower limit of the reference range adjusted serum calcium level 21-23 or S-Ca2 between 105-115mmolL serum phosphate levels within the reference range serum calcium-phosphate product below 44 mmol2l2 55 mg2dl2 24-hurinary calcium excretion 75 mmol2h 300 mg24h in men 625 mmol24h 250 mg24h in women or 01 mmolkg per 24 h 4 mgkg per 24h in both sexes
In addition to hypocalcemia patients affected by chronic hypoparathyroidism have a higher risk of renal implications such as urolithiasis and renal impairment because lack of PTH reduces calcium absorption and phosphate excretion causing hypercalciuria and hyperphosphatemia
Moreover many patients with hypoparathyroidism complain of reduced quality of life QOL in ways that are difficult to quantify but that are nevertheless of concern Biochemical control with standard therapy is rarely accompanied by improved functioning or sense of well-being Complaints of cognitive dysfunction are common with the term brain fog typically described by patients In support of these issues large cohort studies from Denmark have shown increased risk of hospitalization for depression and affective disorders renal impairment and infections whereas the risk for cancer and overall mortality was not increased
According to the European guideline 2015 standard treatment includes oral calcium salts and active vitamin D metabolites to relieve symptoms of hypocalcaemia maintain serum calcium levels in the low normal range and improve the patients QoL An adequate daily intake of calcium from diet and supplements is advisable Different calcium salts are available as supplements because elemental calcium is highly reactive so it has to be combined with other substances These preparations differ in the concentration of elemental calcium per gram
Calcium carbonate is most often used and less expensive than other calcium preparations and contains the highest concentration of elemental calcium per gram 42 It requires gastric hydrochloric acid to form carbonic acid H2CO3 that immediately decomposes into water H2O and carbon dioxide CO2 CO2 is responsible for its side effects such as flatulence constipation and general gastrointestinal disorders Therefore in some patients it is better to find an alternative to calcium carbonate Calcium citrate for example should be recommended to patients with achlorhydria or on treatment with proton pump inhibitors PPI as well as to patients who preferred to take supplements outside mealtimes
Previous studies showed that calcium citrate in comparison to calcium carbonate causes greater increment in serum calcium concentration and urinary calcium excretion in parallel with greater suppression of serum PTH after Roux-en-Y Gastric bypass and this datum suggests both the pharmacokinetic and pharmacodynamic superiority of calcium citrate
Calcium citrate is also better adsorbed than calcium carbonate after panproctocolectomy so in a condition of a general enteric malabsorption
Up to now there are no studies aimed to investigate the efficacy of calcium citrate in the management of subjects with chronic hypoparathyroidism In particular the investigators will test the efficacy of calcium citrate in maintaining normal calcium level compared to carbonate calcium in subjects with chronic hypoparathyroidism Moreover the investigators will evaluate the impact of calcium citrate on QOL in this kind of patients compared to the gold standard therapy carbonate calcium
MATERIALS AND METHODS Each subject will participate in two phases of the study and each phase will last one month Once every 2 weeks blood and a morning urine sample will be drawn For all the study period participants will be instructed to maintain a predetermined dietary calcium intake 800 mgday with sodium 100 mEqday restrictions All subjects will complete a questionnaire on quality of life at 0 2 4 week during both phases The investigators will use the Rand 36-Item Short Form Health Survey version 10 to evaluate the QOL
Phase 1 According to a block randomization scheme subjects will be assigned to a calcium supplement Drug A or Drug B at the same total amount of elemental calcium that they had taken before the study enrollment The dose of Vitamin D will be equal to the daily dose taken prior to the study and will not be changed during the study period
Phase 2 subjects will be shift to the opposite Drug from drug A to drug B or from drug B to drug A at the same total amount of elemental calcium that they had taken during the last week of the phase 1
SAMPLE SIZE CALCULATION
1 Based on the assumption that the within-patient standard deviation of the calcium oxalate saturation is 05 to demonstrate that calcium citrate does not affect the calcium oxalate saturation a total of 24 patients need to be enrolled in this study This sample size will allow to detect a difference of 043 points at a two-sided 5 significance level with a probability of type II error of 20
2 to demonstrate that calcium citrate is as effective as calcium carbonate in maintaining serum Ca within the acceptable clinical range To this end we will study a sample of 21 people already treated with calcium and vitamin D supplementation Our hypothesis is that at the end of the study period the mean Ca concentration will not be different from the ideal value 9 mgdl accepting a 10 variation as the equivalence limit ie accepting as equivalent values between 81 and 99 mgdl Under these assumptions we would need 11 patients to show equivalence between the two treatments with a alpha error probability of 5 and a beta error probability of 1020 With the available sample size we will be able to establish equivalence with an equivalence limit of 07 ie values between 83 and 97 mgdl
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None