Clinical trial NCT03401541: 25-Hydroxyvitamin D Pharmacokinetic Study
Official title: Pilot Clinical Trial to Evaluate the Pharmacokinetics of Orally Administered 25-hydroxyvitamin D3 and Vitamin D3 in Healthy Adults and Adults With a History of Intestinal Malabsorption
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Vitamin D Deficiency
Fat Malabsorption
Keywords: Calcifediol (25(OH)D)
Calciferol (Vitamin D)
Lead sponsor: Boston University
Sponsor class: OTHER
First posted: 2018-01-17
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Each arm will first receive 25(OH)D and then vitamin D or vitamin D and then 25(OH)D
Primary purpose: TREATMENT

Brief summary: To evaluate the pharmacokinetic parameters of orally administered 25-hydroxyvitamin D3 \[25(OH)D3\] and vitamin D3 from the corresponding serum concentration-time curves in healthy adults and adults with a history of intestinal malabsorption.

Detailed description: Patients with a history of intestinal malabsorption (n=10) and healthy volunteers (n=10); (of both sexes and all ethnicities) will be recruited in this randomized double-blind crossover study. All subjects will be prescreened for 25(OH)D levels to include subjects with 25(OH)D\<30 ng/ml. The subjects will be randomized to receive a single oral dose of 900 µg of either vitamin D3 or 25(OH)D3. Blood samples will be taken at baseline and at 2,4,6,8,12 hours and days 1,2,3, 7 and 14. After a washout period of at least 14 days (2 weeks) the subjects will receive in a double blinded manner a single oral dose of 900 µg of either 25(OH)D3 or vitamin D3 (depending on which one they took in the randomization) any time after the washout. Blood samples will be taken at baseline and at 2,4,6,8,12 hours and days 1,2,3,7, 14.

Serum levels of calcium, phosphorus, albumin, creatinine, intact parathyroid hormone (iPTH) will be obtained at baseline and at day 14 (or within a reasonable time if unable to come in on the exact day). Vitamin D and 25(OH)D will be determined on all the blood samples collected at the various times.

Eligibility criteria: Inclusion Criteria:

* Adult male or female with history of intestinal fat-malabsorption with confirmed diagnosis
* Taking vitamin D (ergocalciferol or cholecalciferol). Subjects taking vitamin D supplement of more than 2000 IUs (50 micrograms)/day) that may interfere with study endpoints must be willing and able to discontinue use of these supplements for the duration of the study and allow for at least a 14-day washout prior to prescreening and enrollment.
* Women of child bearing potential must be on birth control and not pregnant based on a negative pregnancy test at baseline for each of the 2 pharmacokinetic studies.
* Serum total 25(OH)D \< 30 ng/mL

Exclusion Criteria:

* Unwilling to discontinue use of supplemental dose of vitamin D2 (ergocalciferol) or vitamin D3 (cholecalciferol) daily equivalent (2,000 IU/50 μg) 1 week or less prior to randomization and during the study
* On medications that can affect vitamin D metabolism including steroids such as prednisone, anti-seizure medications and medications to treat HIV.
* Tanning in a tanning bed at least one week before the study and throughout the duration of this study.
* Anyone anticipating going on holiday (where exposure to sun is imminent) 1 week before or during the entire study.
* Participation in the study or any reason which, in the opinion of the investigator makes adherence to a treatment or follow-up schedule unlikely
* History of elevated serum calcium
* Chronic hepatic or renal failure
* Subjects with a history of an adverse reaction to orally administered vitamin D.
* Inability to give informed consent

Primary outcomes:
measure: Change in Serum vitamin D status
timeFrame: 2 weeks after administration
measure: Change in 25-Hydroxyvitamin D Status
timeFrame: 2 weeks after administration
Secondary outcomes:
measure: Serum Calcium Levels
timeFrame: Baseline and completion of each intervention period (2 weeks)
measure: Serum Phosphorus Levels
timeFrame: Baseline and completion of each intervention period (2 weeks)
measure: Serum Albumin Levels
timeFrame: Baseline and completion of each intervention period (2 weeks)
measure: Serum Creatinine levels
timeFrame: Baseline and completion of each intervention period (2 weeks)
measure: Serum intact parathyroid hormone levels
timeFrame: Baseline and completion of each intervention period (2 weeks)
Other outcomes:
Locations:
city: Boston
country: United States
facility: Solomon Carter Fuller Mental Health Center
state: Massachusetts
Study officials:
affiliation: Boston University
name: Michael F Holick, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Charoenngam N, Kalajian TA, Shirvani A, Yoon GH, Desai S, McCarthy A, Apovian CM, Holick MF. A pilot-randomized, double-blind crossover trial to evaluate the pharmacokinetics of orally administered 25-hydroxyvitamin D3 and vitamin D3 in healthy adults with differing BMI and in adults with intestinal malabsorption. Am J Clin Nutr. 2021 Sep 1;114(3):1189-1199. doi: 10.1093/ajcn/nqab123.