Trial Of Paricalcitol and Cholecalciferol(Vitamin D3) in the Treatment Of Secondary Hyperparathyroidism in Patients After ROUX-EN-Y Gastric Bypass Surgery (ExtenD)

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

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

Study Overview

• Status: Completed
• Conditions: Gastric Bypass; Parathyroid Hormone
• Intervention / Treatment: Drug: Paricalcitol; Drug: Cholecalciferol; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Royal Oak, Michigan, United States, 48073
      • William Beaumont Health Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Paricalcitol; This is a randomized, double-blind, double-dummy, placebo-controlled trial investigating the effects of paricalcitol capsules,cholecalciferol capsules, and matching placebo on PTH level at 6 weeks in patients with sHPT after RYGB. The pool of patients in the Beaumont Bariatric Surgery program will be sufficient to enroll approximately 75 subjects (25 per treatment group).	Drug: Paricalcitol; 1 microgram by mouth daily for 6 weeks
ACTIVE_COMPARATOR: cholecalciferol; This is a randomized, double-blind, double-dummy, placebo-controlled trial investigating the effects of paricalcitol capsules, cholecalciferol capsules, and matching placebo on PTH level at 6 weeks in patients with sHPT after RYGB. The pool of patients in the Beaumont Bariatric Surgery program will be sufficient to enroll approximately 75 subjects (25 per treatment group).	Drug: Cholecalciferol; 5000 IU (international units) by mouth daily for 6 weeks
PLACEBO_COMPARATOR: placebo; This is a randomized, double-blind, double-dummy, placebo-controlled trial investigating the effects of paricalcitol capsules, cholecalciferol capsules, and matching placebo on PTH level at 6 weeks in patients with sHPT after RYGB. The pool of patients in the Beaumont Bariatric Surgery program will be sufficient to enroll approximately 75 subjects (25 per treatment group).	Drug: Placebo; Inactive substance, one capsule daily for 6 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	6 weeks
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	6 weeks
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	6 weeks
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	6 weeks
Osteocalcin	This secondary outcome measure is change in osteocalcin from baseline to final measure at 6 weeks differences in the 3 arms were compared	6 weeks
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	6 weeks
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	6 weeks
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	6 weeks

Collaborators and Investigators

• Sponsor: Kerstyn C. Zalesin, M.D.
• Collaborators: Abbott
• Investigators: Principal Investigator: Kerstyn Zalesin, MD, William Beaumont Hospitals

Study record dates

Study Major Dates

• Study Start: July 1, 2010
• Primary Completion (ACTUAL): August 1, 2015
• Study Completion (ACTUAL): August 1, 2015

Study Registration Dates

• First Submitted: June 4, 2010
• First Submitted That Met QC Criteria: June 4, 2010
• First Posted (ESTIMATE): June 7, 2010

Study Record Updates

• Last Update Posted (ACTUAL): March 22, 2017
• Last Update Submitted That Met QC Criteria: February 1, 2017
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Keywords: vitamin D; paricalcitol; Gastric bypass surgery; PTH
• Additional Relevant MeSH Terms: Endocrine System Diseases; Parathyroid Diseases; Hyperparathyroidism; Hyperparathyroidism, Secondary; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol
• Other Study ID Numbers: 2009-234

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO