Clinical trial NCT01138475: Trial Of Paricalcitol and Cholecalciferol(Vitamin D3) in the Treatment Of Secondary Hyperparathyroidism in Patients After ROUX-EN-Y Gastric Bypass Surgery
Official title: A Prospective, Randomized, Double-Blind, Double-Dummy,Placebo-Controlled, Parallel-Group, Pilot Trial Of Paricalcitol and Cholecalciferol(Vitamin D3) in the Treatment Of Secondary Hyperparathyroidism in Patients After ROUX-EN-Y Gastric Bypass Surgery
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Gastric Bypass
Parathyroid Hormone
Keywords: PTH
Gastric bypass surgery
vitamin D
paricalcitol
Lead sponsor: William Beaumont Hospitals
Sponsor class: OTHER
Collaborators: name: Abbott
First posted: 2010-06-07
Enrollment: 49
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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.

Primary outcomes:
measure: The Primary Outcome Measure With iPTH
timeFrame: 6 weeks
Secondary outcomes:
measure: Alkaline Phosphatase
timeFrame: 6 weeks
measure: Serum Calcium
timeFrame: 6 weeks
measure: Serum 25 OH Vitamin D
timeFrame: 6 weeks
measure: Serum Phosphorus
timeFrame: 6 weeks
measure: Osteocalcin
timeFrame: 6 weeks
measure: N-Telopeptide Cross Linked Urine
timeFrame: 6 weeks
measure: Bone Specific Alkaline Phosphatase
timeFrame: 6 weeks
measure: 24 Hour Urine Calcium
timeFrame: 6 weeks
Other outcomes:
Locations:
city: Royal Oak
country: United States
facility: William Beaumont Health Center
state: Michigan
Study officials:
affiliation: William Beaumont Hospitals
name: Kerstyn Zalesin, MD
role: PRINCIPAL_INVESTIGATOR
References: