Gastric Bypass, Parathyroid Hormone
Conditions
Keywords
PTH, Gastric bypass surgery, vitamin D, paricalcitol
Brief summary
Evaluate the efficacy of paricalcitol, cholecalciferol, and placebo in the reduction of parathyroid hormone in patients after Roux-en-Y gastric bypass surgery (RYGB). Assess changes, if any, in measures of self-assessed well-being attributable to paricalcitol after RYGB. Evaluate the rates of hypercalcemia, kidney stones, gastrointestinal side effects, and other organ system adverse effects of paricalcitol, cholecalciferol, and placebo in patients after RYGB
Interventions
DRUGParicalcitol
1 microgram by mouth daily for 6 weeks
DRUGCholecalciferol
5000 IU (international units) by mouth daily for 6 weeks
DRUGPlacebo
Inactive substance, one capsule daily for 6 weeks
Sponsors
Abbott
Kerstyn C. Zalesin, M.D.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
Yes
Inclusion criteria
* 1\. Subject has voluntarily signed and dated an informed consent form, approved by an Institutional Review Board (IRB), after the nature of the study has been explained and the subject has had the opportunity to ask questions. The informed consent must be signed before any study-specific procedures are performed. 2\. Must be post bariatric (\> 6 weeks and ≤ 5 years) Rou-en-Y gastric bypass surgical patient. 3\. Male or female subjects \> 18 years. 4. For entry into the Treatment Period the subject must satisfy the following criteria based on the existing laboratory values previously drawn on clinical grounds: * Serum calcium level 8.0-10.5 mg/dL * Phosphorous level \< 5.2 mg/dL (1.68 mmol/L) * Serum albumin \> 3.0 g/dL (30 g/L). 5. For entry into the Treatment Period the subject must satisfy the following criteria based on screening laboratories (Beaumont Reference Laboratories, screening laboratory values are not blinded): * iPTH \> 69 pg/ml * Negative serum pregnancy test for female subjects of childbearing potential. 6. In the opinion of the investigator, the subject must be receiving optimal medical management of other co morbidities including but not limited to HTN, DM, CVD, liver disease, and lung disease. 7\. If female, subject is not breast feeding or is not pregnant (verified by negative pregnancy test prior to the Treatment Period); or is not of childbearing potential, defined as postmenopausal for at least one year or surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy); or is of childbearing potential and practicing one of the following methods of birth control: * Double-barrier method (any two of the following: condoms, contraceptive sponge, diaphragm, vaginal ring with spermicidal jellies or creams, or intrauterine device \[IUD\]) * Hormonal contraceptives (oral, parenteral, or transdermal) for at least three months prior to and during study drug administration * Maintains a monogamous relationship with a vasectomized partner * Total abstinence from sexual intercourse during the study (minimum one complete menstrual cycle prior to study start)
Exclusion criteria
* . Subject has previously been on active vitamin D therapy (calcitriol, paricalcitol, doxercalciferol, alfacalcidol) within the 30-day washout period prior to the Treatment Period at doses greater than 1200 IU of vitamin D3 or equivalent. 2\. Subject has a history of an allergic reaction or significant sensitivity to paricalcitol or to drugs similar to the study drug (i.e., vitamin D or vitamin D related compounds). 3\. Pregnant (confirmed by screening pregnancy test) or lactating females. 4. Subject is expected to initiate renal replacement therapy within one year. 5. Known history of hypercalcemia (\>10.5 mg/dl), hyperphosphatemia (\>6 mg/dl) primary hyperparathyroidism, or history of end-stage renal disease requiring renal replacement therapy. 6\. Full remission from a malignancy for less than one year (except completely excised non-Melanoma skin cancer e.g., basal or squamous carcinoma) or any history of bone metastasis. 7\. Subject has co-morbid conditions (e.g., advanced malignancy, advanced liver disease) with a life expectancy less than 1 year. 8\. Subject has received any investigational drug within 30 days prior to study drug administration or is currently enrolled in another clinical trial. 9\. Subject has a history of active kidney stones within the 2 years prior to the Screening Period. 10\. Subject has poorly controlled hypertension (systolic blood pressure \> 180 mmHg and/or diastolic blood pressure \> 110 mmHg at the Screening Visit (confirmed by repeat). 11\. Subject has history of renal artery stenosis, primary aldosteronism or pheochromocytoma, 12. Subject is taking calcitonin, bisphosphonates, cinacalcet, glucocorticoids (except topical or inhaled glucocorticoids), or other drugs that may affect calcium or bone metabolism, other than aluminum, calcium and non-calcium containing phosphate binders or female subjects on stable (same dose and product for three months) estrogen and/or progestin therapy. 13\. Subject is currently receiving immunosuppressant therapy and/or high doses (non-maintenance therapy) of glucocorticoids (\> 5 mg/day of prednisone or equivalent). 14\. Subject has had acute renal failure within 12 weeks of the Screening Phase defined by an acute rise in serum Cr (of at least 0.5 mg/dL or 44 micromoles/L) to more than 4 g/dL (350 micromoles/L). 15\. Subject is known to be HIV positive. 16. Use of known inhibitors (i.e., ketoconazole) or inducers (i.e., carbamazepine) of cytochrome P450 3 A (CYP3 A) within two weeks prior to study drug administration. 17\. For any reason, subject is considered by the Investigator to be an unsuitable candidate to receive paricalcitol capsules or is put at risk by study procedures. 18\. Subject has a history of drug or alcohol abuse within six months prior to screening. 19\. Subject has had a liver or kidney transplant. 20. Stage V CKD subjects on renal replacement therapy are explicitly excluded. 21. Subject has had a CVA within the last 3 months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Primary Outcome Measure With iPTH | 6 weeks | Change in iPTH was compared in each arm from baseline to final measure at 6 weeks the differences were compared in the 3 arms of the study |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum Calcium | 6 weeks | This secondary outcome measure is change in serum calcium from baseline to final measure at 6 weeks differences in the 3 arms were compared |
| Serum 25 OH Vitamin D | 6 weeks | This secondary outcome measure is change in serum hydroxy-vitaminD from baseline to final measure at 6 weeks differences in the 3 arms were compared |
| Serum Phosphorus | 6 weeks | This secondary outcome measure is change in serum phosphorus from baseline to final measure at 6 weeks differences in the 3 arms were compared |
| Alkaline Phosphatase | 6 weeks | This secondary outcome measure is change in alkaline phosphatase from baseline to final measure at 6 weeks differences were compared between the 3 arms of the study |
| N-Telopeptide Cross Linked Urine | 6 weeks | This secondary outcome measure is change in N-Telopeptide cross linked urine from baseline to final measure at 6 weeks, differences in the 3 arms were compared |
| Bone Specific Alkaline Phosphatase | 6 weeks | This secondary outcome measure is change in bone specific alkaline phosphatase from baseline to final measure at 6 weeks, differences in the 3 arms were compared |
| 24 Hour Urine Calcium | 6 weeks | This secondary outcome measure is change in 24-hour urine calcium from baseline to final measure at 6 weeks, differences in the 3 arms were compared |
| Osteocalcin | 6 weeks | This secondary outcome measure is change in osteocalcin from baseline to final measure at 6 weeks differences in the 3 arms were compared |
Countries
United States
Participant flow
Recruitment details
Subjects have been recruited from our patients who underwent gastric bypass surgery. They needed to be able to give informed consent, age \> 18 years, within 12 months of RYGB being performed, post-operative iPTH \>69 pg/ml negative serum pregnancy test, serum calcium 8.0-10.5 mg/dl, phosphorus level \<5.2 mg/dl, and serum albumin \>3.0 g/dl.
Participants by arm
| Arm | Count |
|---|---|
| Paricalcitol | 16 |
| Cholecalciferol | 17 |
| Placebo | 16 |
| Total | 49 |
Baseline characteristics
| Characteristic | Paricalcitol | Cholecalciferol | Placebo | Total |
|---|---|---|---|---|
| 24 hour urine calcium | 89 mmol STANDARD_DEVIATION 81 | 106 mmol STANDARD_DEVIATION 139 | 131 mmol STANDARD_DEVIATION 91 | 109 mmol STANDARD_DEVIATION 105 |
| 25 OH vitamin D | 30 ng/dL STANDARD_DEVIATION 16 | 32 ng/dL STANDARD_DEVIATION 13 | 30 ng/dL STANDARD_DEVIATION 7 | 30 ng/dL STANDARD_DEVIATION 12 |
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 16 Participants | 17 Participants | 16 Participants | 49 Participants |
| Age, Continuous | 55 years STANDARD_DEVIATION 9 | 55 years STANDARD_DEVIATION 10 | 51 years STANDARD_DEVIATION 11 | 53.8 years STANDARD_DEVIATION 9.9 |
| alkaline phosphatase | 87 u/L STANDARD_DEVIATION 19 | 97 u/L STANDARD_DEVIATION 29 | 101 u/L STANDARD_DEVIATION 32 | 95 u/L STANDARD_DEVIATION 27 |
| bone specific alkaline phosphatase | 15 U/L STANDARD_DEVIATION 5 | 19 U/L STANDARD_DEVIATION 8.1 | 19 U/L STANDARD_DEVIATION 10 | 18 U/L STANDARD_DEVIATION 8.2 |
| osteocalcin | 39 ng/mL STANDARD_DEVIATION 19 | 36 ng/mL STANDARD_DEVIATION 17 | 40 ng/mL STANDARD_DEVIATION 20 | 39 ng/mL STANDARD_DEVIATION 19 |
| PTH | 96 ng/mL STANDARD_DEVIATION 27 | 90 ng/mL STANDARD_DEVIATION 15 | 101 ng/mL STANDARD_DEVIATION 25 | 96 ng/mL STANDARD_DEVIATION 24 |
| Region of Enrollment United States | 16 participants | 17 participants | 17 participants | 49 participants |
| serum calcium | 9.4 mg/dL STANDARD_DEVIATION 0.3 | 9.3 mg/dL STANDARD_DEVIATION 0.3 | 9.4 mg/dL STANDARD_DEVIATION 0.4 | 9.3 mg/dL STANDARD_DEVIATION 0.3 |
| serum phosphorous | 3.9 mg/dL STANDARD_DEVIATION 0.6 | 3.7 mg/dL STANDARD_DEVIATION 0.5 | 3.7 mg/dL STANDARD_DEVIATION 0.5 | 3.7 mg/dL STANDARD_DEVIATION 0.5 |
| Sex: Female, Male Female | 15 Participants | 11 Participants | 15 Participants | 41 Participants |
| Sex: Female, Male Male | 1 Participants | 6 Participants | 1 Participants | 8 Participants |
| Urine N-telopeptide cross linked | 64 nmol STANDARD_DEVIATION 26 | 73 nmol STANDARD_DEVIATION 30 | 82 nmol STANDARD_DEVIATION 55 | 73 nmol STANDARD_DEVIATION 40 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 16 | 0 / 17 | 0 / 16 |
| serious Total, serious adverse events | 0 / 16 | 0 / 17 | 0 / 16 |
Outcome results
Primary
The Primary Outcome Measure With iPTH
Change in iPTH was compared in each arm from baseline to final measure at 6 weeks the differences were compared in the 3 arms of the study
Time frame: 6 weeks
Population: missing data in paricalcitol and placebo group
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paricalcitol | The Primary Outcome Measure With iPTH | 72 pg/mL | Standard Deviation 31 |
| Cholecalciferol | The Primary Outcome Measure With iPTH | 87 pg/mL | Standard Deviation 43 |
| Placebo | The Primary Outcome Measure With iPTH | 82 pg/mL | Standard Deviation 30 |
Secondary
24 Hour Urine Calcium
This secondary outcome measure is change in 24-hour urine calcium from baseline to final measure at 6 weeks, differences in the 3 arms were compared
Time frame: 6 weeks
Population: Missing data from paricalcitol and cholecalciferol arms
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paricalcitol | 24 Hour Urine Calcium | 132 mg/dL | Standard Deviation 126 |
| Cholecalciferol | 24 Hour Urine Calcium | 101 mg/dL | Standard Deviation 111 |
| Placebo | 24 Hour Urine Calcium | 135 mg/dL | Standard Deviation 81 |
Secondary
Alkaline Phosphatase
This secondary outcome measure is change in alkaline phosphatase from baseline to final measure at 6 weeks differences were compared between the 3 arms of the study
Time frame: 6 weeks
Population: missing 1 participant data in the paricalcitol group
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paricalcitol | Alkaline Phosphatase | 87 U/L | Standard Deviation 22 |
| Cholecalciferol | Alkaline Phosphatase | 94 U/L | Standard Deviation 24 |
| Placebo | Alkaline Phosphatase | 101 U/L | Standard Deviation 33 |
Secondary
Bone Specific Alkaline Phosphatase
This secondary outcome measure is change in bone specific alkaline phosphatase from baseline to final measure at 6 weeks, differences in the 3 arms were compared
Time frame: 6 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paricalcitol | Bone Specific Alkaline Phosphatase | 15 u/L | Standard Deviation 4.8 |
| Cholecalciferol | Bone Specific Alkaline Phosphatase | 19 u/L | Standard Deviation 7 |
| Placebo | Bone Specific Alkaline Phosphatase | 18 u/L | Standard Deviation 5 |
Secondary
N-Telopeptide Cross Linked Urine
This secondary outcome measure is change in N-Telopeptide cross linked urine from baseline to final measure at 6 weeks, differences in the 3 arms were compared
Time frame: 6 weeks
Population: Missing data from cholecalciferol and placebo participant arms
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paricalcitol | N-Telopeptide Cross Linked Urine | 74 nmol | Standard Deviation 29 |
| Cholecalciferol | N-Telopeptide Cross Linked Urine | 67 nmol | Standard Deviation 34 |
| Placebo | N-Telopeptide Cross Linked Urine | 77 nmol | Standard Deviation 36 |
Secondary
Osteocalcin
This secondary outcome measure is change in osteocalcin from baseline to final measure at 6 weeks differences in the 3 arms were compared
Time frame: 6 weeks
Population: Missing data from all 3 participant arms
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paricalcitol | Osteocalcin | 38 ng/mL | Standard Deviation 21 |
| Cholecalciferol | Osteocalcin | 39 ng/mL | Standard Deviation 20 |
| Placebo | Osteocalcin | 42 ng/mL | Standard Deviation 21 |
Secondary
Serum 25 OH Vitamin D
This secondary outcome measure is change in serum hydroxy-vitaminD from baseline to final measure at 6 weeks differences in the 3 arms were compared
Time frame: 6 weeks
Population: missing data from participant in paricalcitrol arm
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paricalcitol | Serum 25 OH Vitamin D | 27 ng/dL | Standard Deviation 7.2 |
| Cholecalciferol | Serum 25 OH Vitamin D | 38 ng/dL | Standard Deviation 15 |
| Placebo | Serum 25 OH Vitamin D | 25 ng/dL | Standard Deviation 7.8 |
Secondary
Serum Calcium
This secondary outcome measure is change in serum calcium from baseline to final measure at 6 weeks differences in the 3 arms were compared
Time frame: 6 weeks
Population: missing data from participant in paricalcitrol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paricalcitol | Serum Calcium | 9.3 mg/dL | Standard Error 0.3 |
| Cholecalciferol | Serum Calcium | 9.4 mg/dL | Standard Error 0.3 |
| Placebo | Serum Calcium | 9.3 mg/dL | Standard Error 0.6 |
Secondary
Serum Phosphorus
This secondary outcome measure is change in serum phosphorus from baseline to final measure at 6 weeks differences in the 3 arms were compared
Time frame: 6 weeks
Population: missing data from all 3 participant arms
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paricalcitol | Serum Phosphorus | 4.0 mg/dL | Standard Deviation 0.3 |
| Cholecalciferol | Serum Phosphorus | 3.4 mg/dL | Standard Deviation 0.5 |
| Placebo | Serum Phosphorus | 3.7 mg/dL | Standard Deviation 0.7 |