PK/PD of Vitamin D3 in Adults With CF

Cystic Fibrosis Clinical Trial

Official title:

A Pilot Study Evaluating Single, High-dose Pharmacokinetics/Pharmacodynamics of Vitamin D3 in CF

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03734744
• Other study ID #: HS-18-00737
• Status: Terminated
• Phase: N/A
• Start date: June 17, 2019
• Est. completion date: May 16, 2022

Study information

• Verified date: May 2022
• Source: University of Southern California
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Despite the extensive literature on adverse clinical outcomes associated with vitamin D deficiency, there are currently no proven treatment strategy that effectively achieves and maintains optimal serum vitamin D status in cystic fibrosis (CF) patients. For the treatment of vitamin D deficiency, CF Foundation currently recommends 2,000 IU daily. However, because achieving adequate serum 25(OH)D levels is a challenge in CF, higher doses of vitamin D may be necessary to reach and maintain vitamin D sufficiency. Poor oral bioavailability of ergocalciferol has been demonstrated in CF patients, which may potentially also be an issue with cholecalciferol. In order to optimize the treatment of vitamin D deficiency in CF, the kinetic disposition must be well understood. However, there are very few data currently available describing the kinetics of both vitamin D and 25-hydroxyvitamin D, and to the investigator's knowledge, no studies have yet characterized the pharmacokinetic disposition of vitamin D and its metabolites in cystic fibrosis. Addressing this issue is crucial in effectively and safely correcting vitamin D deficiency in CF.

Description:

Clinically stable CF patients with a history of pancreatic insufficiency (n=6) and matching non-CF subjects (n=6) will be recruited in this study. All subjects will be pre-screened for 25(OH)D status to include those with 25(OH)D levels below 30 ng/mL. The subjects will receive a single oral dose (300,000 - 600,000 IU) of vitamin D3, and the dose will be based on study participant's baseline 25-hydroxyvitamin D3 level. For CF patients, the dose will be administered with food and pancreatic enzyme supplement. This dose was chosen as previous studies in pediatric CF patients demonstrated that a large single dose of up to 600,000 IU vitamin D3 raised and maintained sufficient 25(OH)D concentrations without any signs of adverse events.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 6
• Est. completion date: May 16, 2022
• Est. primary completion date: May 16, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• For CF, diagnosis of CF based on positive sweat chloride or known CF mutation
• For CF, Patients with pancreatic insufficiency
• Age = 18 years
• Serum 25(OH)D concentrations below 30 ng/mL (75 nmol/L)

Exclusion Criteria:

• Pregnancy
• History of lung transplant,
• Severe anemia (hemoglobin concentration < 7 g/dL),
• Liver disease (AST/ALT > 3x ULN), kidney disease (GFR = 40 mL/min), or granulomatous conditions
• Patients taking steroids, cholesterol-lowering drug (cholestyramine), weight-loss drugs (orlistat) , statins, anti-tuberculosis drugs (rifampin and isoniazid), phenobarbital, phenytoin, carbamazepine, immunosuppressants (cyclosporine, tacrolimus)

Related Conditions & MeSH terms

• Cystic Fibrosis
• Vitamin D Deficiency

Intervention

Dietary Supplement:
• Vitamin D3
Vitamin D is a fat-soluble vitamin that plays an important role in immune modulation in addition to its classical roles in regulation of calcium homeostasis and bone health

Locations

Country	Name	City	State
United States	Keck Hospital of University of Southern California	Los Angeles	California

Sponsors (1)

Lead Sponsor	Collaborator
University of Southern California

Country where clinical trial is conducted

United States, 

References & Publications (5)

Grossmann RE, Zughaier SM, Kumari M, Seydafkan S, Lyles RH, Liu S, Sueblinvong V, Schechter MS, Stecenko AA, Ziegler TR, Tangpricha V. Pilot study of vitamin D supplementation in adults with cystic fibrosis pulmonary exacerbation: A randomized, controlled trial. Dermatoendocrinol. 2012 Apr 1;4(2):191-7. doi: 10.4161/derm.20332. — View Citation

Lark RK, Lester GE, Ontjes DA, Blackwood AD, Hollis BW, Hensler MM, Aris RM. Diminished and erratic absorption of ergocalciferol in adult cystic fibrosis patients. Am J Clin Nutr. 2001 Mar;73(3):602-6. — View Citation

Shepherd D, Belessis Y, Katz T, Morton J, Field P, Jaffe A. Single high-dose oral vitamin D3 (stoss) therapy--a solution to vitamin D deficiency in children with cystic fibrosis? J Cyst Fibros. 2013 Mar;12(2):177-82. doi: 10.1016/j.jcf.2012.08.007. Epub 2012 Sep 19. — View Citation

Tangpricha V, Kelly A, Stephenson A, Maguiness K, Enders J, Robinson KA, Marshall BC, Borowitz D; Cystic Fibrosis Foundation Vitamin D Evidence-Based Review Committee. An update on the screening, diagnosis, management, and treatment of vitamin D deficiency in individuals with cystic fibrosis: evidence-based recommendations from the Cystic Fibrosis Foundation. J Clin Endocrinol Metab. 2012 Apr;97(4):1082-93. doi: 10.1210/jc.2011-3050. Epub 2012 Mar 7. — View Citation

Thacher TD, Clarke BL. Vitamin D insufficiency. Mayo Clin Proc. 2011 Jan;86(1):50-60. doi: 10.4065/mcp.2010.0567. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Peak plasma concentrations (Cmax)		10 weeks
Primary	Time taken to reach the maximum concentration (Tmax)		10 weeks
Primary	Area under the plasma concentration versus time curve (AUC)		10 weeks
Secondary	Levels of serum inflammatory biomarkers	Changes in IL-6, IL-8, TNF-a, IL-1ß, C-reactive protein	10 weeks