Vitamin D and Coronary Calcification Study

NCT00752102 | Completed Phase 4 Results

• 1 other identifier: Abbott #20128
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

Patients with chronic kidney disease (CKD) have a higher mortality rate than the general population, with cardiovascular disease (CVD) accounting for approximately 50% of deaths. Vascular calcification is a common finding in patients with CKD. Furthermore, patients with CKD develop secondary hyperparathyroidism, partly because of a decrease of calcitriol synthesis on the kidney. Treatment of secondary hyperparathyroidism includes use of activated vitamin D including calcitriol and paricalcitol. Recent evidence in dialysis patients suggest an improved survival in patients using paricalcitol compared to calcitriol. Studies in uremic rats suggests that there are differential effects of calcitriol and paricalcitol in expression of markers of soft-tissue calcification independent of calcium-phosphorus product. Calcitriol increased calcification of vascular smooth muscle cells cultured in calcification media. There was also significant increase in pulse pressure in animals treated with calcitriol. The investigators hypothesize that these different forms of vitamin D may have differential effects in vascular calcification progression in CKD patients.

Conditions

Chronic Kidney Disease; Vitamin D Deficiency; Coronary Calcification; Disorders of Calcium and Bone Metabolism

Keywords

Secondary Hyperparathryoidism; Chronic Kidney Disease; Vitamin D; Coronary Calcification; Bone metabolism

Outcome Measures

Primary Outcomes (1)

• Coronary Artery (CAC) Score Progression

  coronary artery (CAC) score difference between baseline and followup CT scans. It was measured in Agatston units. These are units of amount of calcification in the blood vessels so it's a continuous variable. The amount of calcium was quantified with the Agatston scoring method. Calcium scores were adjusted with a standard calcium phantom that was scanned along with the participant. The phantom contained known calcium density bars and provided a way to calibrate the x-ray attenuation level. Participants scoring CAC \>400 are considered to be at risk for having at least one coronary lesion.

  48 weeks

Study Arms (2)

Calcitriol

ACTIVE COMPARATOR

Calcitriol is a synthetic vitamin D analog which is active in the regulation of the absorption of calcium from the gastrointestinal tract and its utilization in the body. Calcitriol is available as capsules containing 0.25 mcg or 0.5 mcg calcitriol and as an oral solution containing 1 mcg/ml of calcitriol. All dosage forms contain butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) as antioxidants. Subjects taking calcitriol started at 0.25 mcg 3x/week and titrated up during the next visit according to PTH levels.

Drug: Calcitriol (Rocaltrol®)

Paricalcitol

ACTIVE COMPARATOR

Paricalcitol, USP, the active ingredient in Zemplar® Capsules, is a synthetically manufactured analog of calcitriol, the metabolically active form of vitamin D indicated for the prevention and treatment of secondary hyperparathyroidism in chronic kidney disease. Zemplar is available as soft gelatin capsules for oral administration containing 1 mcg, 2 mcg or 4 mcg of paricalcitol. Each capsule also contains medium chain triglycerides, alcohol, and butylated hydroxytoluene. Subjects taking paricalcitol will be started at 2 mcg 3x/week and titrated up during the next visit according to PTH levels.

Drug: Paricalcitol

Interventions

Calcitriol (Rocaltrol®) DRUG

Subjects taking calcitriol will be started at 0.25 mcg 3x/week and titrated up during the next visit according to PTH levels. If at the 12 week visit, PTH is still not at goal, then calcitriol will be increased to 0.5 mcg 3x/week.

Also known as: Calcijex®, Rocaltrol®

Calcitriol

Paricalcitol DRUG

Subjects taking paricalcitol will be started at 2 mcg 3x/week and titrated up during the next visit according to PTH levels. If at the 12 week visit, PTH is still not at goal, then paricalcitol will be increased to 4 mcg 3x/week.

Also known as: Zemplar®

Paricalcitol

Eligibility Criteria

• Age: 25 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• CKD stages 3 or 4 (estimated glomerular filtration rate (eGFR) between 15 and 59)
• Diagnosis of secondary hyperparathyroidism, which is defined as:
• Elevated intact PTH (iPTH) as per KDIGO guidelines:
• CKD stage 3 (eGFR 30-59) or CKD stage 4 (eGFR 15-29) with iPTH \> Upper Limit of Normal for lab (6.8 pmol/L)
• Presence of Coronary Artery Calcium (CAC \> 0)
• Subject will be able to complete the study, to the best of his/her knowledge

You may not qualify if:

• iPTH \>1500 pg/ml
• Current or previous use of bisphosphonates
• History of parathyroidectomy or anticipated parathyroidectomy
• History of cinacalcet use
• History of a solid organ transplant or scheduled date for transplant surgery
• History of coronary revascularization (coronary artery bypass surgery or percutaneous intervention)
• History of coronary artifact (e.g. pacemaker, intracardiac defibrillator, artificial valve or biventricular leads)
• Active atrial fibrillation
• Weight greater than 300 pounds (due to limitations of equipment)
• HIV positive
• Current pregnancy (although pregnancy is very rare in the CKD population)
• Life expectancy less than two years as judged by primary physician
• Institutionalized patients (nursing home or prisoners)
• Language barrier or mental incapacity to consent
• Inability to swallow tablets or current gastrointestinal disorder that may be associated with impaired absorption of orally administered medications.

Sponsors & Collaborators

• Joslin Diabetes Center: lead
• Abbott: collaborator

Study Sites (1)

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19107, United States

Location

Related Publications (1)

• Anis KH, Pober D, Rosas SE. Vitamin D Analogues and Coronary Calcification in CKD Stages 3 and 4: A Randomized Controlled Trial of Calcitriol Versus Paricalcitol. Kidney Med. 2020 Jun 17;2(4):450-458. doi: 10.1016/j.xkme.2020.05.009. eCollection 2020 Jul-Aug.

  PMID: 32775985 DERIVED

MeSH Terms

Conditions

Renal Insufficiency, Chronic; Vitamin D Deficiency

Interventions

Calcitriol; paricalcitol

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Avitaminosis; Deficiency Diseases; Malnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Dihydroxycholecalciferols; Hydroxycholecalciferols; Cholecalciferol; Cholestenes; Cholestanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Sterols; Vitamin D; Secosteroids; Membrane Lipids; Lipids

Results Point of Contact

• Title: Dr. Sylvia Rosas
• Organization: Joslin Diabetes Center

sylvia.rosas@joslin.harvard.edu

617-309-2477

Study Officials

• Sylvia E Rosas, MD, MSCE

  Joslin Diabetes Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 11, 2008
• First Posted: September 15, 2008
• Study Start: September 1, 2008
• Primary Completion: October 1, 2013
• Study Completion: October 1, 2013
• Last Updated: December 8, 2017
• Results First Posted: December 8, 2017

Record last verified: 2017-12

Locations

US (1)