Can Biotin Supplementation be Used to Mask hCG Abuse?

Sponsor

Sports Medicine Research and Testing Laboratory (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05450900

Collaborator

(none)

Enrollment

Location

Arms

5.8

Anticipated Duration (Months)

2.1

Patients Per Site Per Month

Study Details

Study Description

Brief 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:

Urinary/serum hCG (human chorionic gonadotropin) and urinary biotin concentrations in both treatment groups before, during, and after hCG intervention using standard immunoassay methods
To monitor hCG in both treatment groups before and after diafiltration of urine samples prior to analysis
To compare urinary and serum detectability (detection window, sensitivity) of hCG abuse in the hCG-only group compared to the hCG + biotin group

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: Choriogonadotropin Alpha Dietary Supplement: biotin Other: Microcellulose filler	Early Phase 1

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

12 participants

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 placeboOne cohort receives active drug ovidrel plus biotin supplementation One cohort receives active drug ovidrel plus a placebo

Masking:

Single (Participant)

Masking Description: