Can Biotin Supplementation be Used to Mask hCG Abuse?
Condition: Healthy
Study type: Interventional
Phase: Early Phase 1

Summary: 
      This sponsor is an anti-doping laboratory tasked with testing athlete samples for prohibited
      substances by the World Anti-Doping Agency and other agencies.

      This study is intended to measure:

        1. Urinary/serum hCG (human chorionic gonadotropin) and urinary biotin concentrations in
           both treatment groups before, during, and after hCG intervention using standard
           immunoassay methods

        2. To monitor hCG in both treatment groups before and after diafiltration of urine samples
           prior to analysis

        3. To compare urinary and serum detectability (detection window, sensitivity) of hCG abuse
           in the hCG-only group compared to the hCG + biotin group
    

Detailed description: 
      hCG, or human chorionic gonadotropin, is a protein hormone primarily produced in females by
      trophoblast cells during early pregnancy. hCG belongs to the glycoprotein hormone (GPH)
      family and exists as a heterodimer with an alpha and beta subunit. Its beta subunit is unique
      to hCG, however, its alpha subunit is identical to that of other GPH family members,
      including luteinizing hormone (LH), follicular stimulating hormone (FSH), and thyroid
      stimulating hormone (TSH). Due to this similarity to FSH and LH, it can be used as a female
      fertility treatment, however, hCG can also also stimulate the production of testosterone in
      the male testes and is sometimes used as a treatment for certain cases of hypogonadism.
      Unfortunately, this activity has led to hCG abuse by male athletes as a method to increase
      endogenous testosterone levels despite being listed as a prohibited substance for male
      athletes by the World Anti-Doping Agency (WADA).

      While most anti-doping testing is conducted using mass spectrometric methods, hCG testing is
      conducted on immunoassay platforms that utilize biotin-streptavidin binding methods
      (automated analyzers, ELISA). Biotin interference is a well-known confounding factor in
      biotin-streptavidin immunoassays. Excess biotin in urine or serum binds to streptavidin
      molecules lowering the sensitivity of the assay. In certain clinical tests that utilize
      biotin-streptavidin binding, excess biotin can impact immunoassay results in individuals
      supplementing with biotin at a dose as low as 5 mg/day. Biotin, or vitamin B7, is a coenzyme
      involved in metabolic processes related to the breakdown of macronutrients. Biotin
      supplementation is considered safe and non-toxic even at remarkably high doses (<300mg/day)
      and it is readily available over the counter. Knowing that biotin supplementation is readily
      available and may be widely used, it is presumable that heavy biotin supplementation may mask
      illicit hCG use by athletes. To overcome this interference in a clinical setting, a method
      utilizing streptavidin coated microparticles has been developed to deplete biotin from
      samples, however this method is costly and not suitable for anti-doping applications.

      The goal of this study is to understand whether hCG use can be masked by over-the-counter
      biotin supplementation, and whether the diafiltration method identified by Sobolevsky and
      Ahrens is a viable protocol for increased accuracy of hCG testing in urine samples.
      Additionally, we aim to understand how this potential masking effect is observed in serum
      samples verses urine samples as biotin is primarily excreted in urine so biotin levels are
      typically lower in the serum when compared to urine. The study will be conducted in male
      participants and will include two groups: hCG +oral biotin treatment and hCG + oral placebo
      treatment. Participants will have seven hCG injections and will be taking an over-the-counter
      biotin (or placebo) supplement daily from the onset of the study until the final day, 32 days
      after the first injection.

      Experimental Design

      Study Drug choriogonadotropin alfa Dose: 250 µg (should equate to between 2000-2300 IU), 2X
      per week, subcutaneously

      Dietary Supplement:

      Biotin (20mg), 1x per day, p.o.

      Placebo Supplement:

      Capsules provided by pharmacy, 1x per day, p.o.

      Study Design

      Subjects will be divided into two treatment groups:

      Cohort 1: hCG treatment, oral biotin supplement Cohort 2: hCG treatment, oral placebo
      supplement As enrollment occurs, participants will be randomized evenly into one of the two
      cohorts in 'every other' fashion.
    

Intervention name(s): Choriogonadotropin Alpha; biotin; Microcellulose filler
Intervention type(s): Drug; Dietary Supplement; Other
Intervention description(s): drug, active; supplement, oral; supplement, oral
Other intervention name(s): ovidrel; hCG; vitamin B7; placebo, capsules
Intervention MeSH terms: Biotin; Chorionic Gonadotropin
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: One cohort receives active drug ovidrel plus biotin supplementation One cohort receives active drug ovidrel plus a placebo
Masking: Single (Participant)
Primary purpose: Other