Clinical trial NCT00489372: Se-Methyl-Seleno-L- Cysteine (MSC) in Treating Healthy Patients
Official title: Phase I Study of Single Oral Dose of Se-Methyl-Seleno-L-Cysteine (MSC) in Adult Men
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy, no Evidence of Disease
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2007-06-21
Enrollment: 36
Sex: MALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This randomized phase I trial is studying the side effects and best dose of Se-methyl-seleno-L-cysteine in healthy adult men. Studying samples of blood, urine, and toenail clippings in the laboratory from healthy men receiving Se-methyl-seleno-L-cysteine may help doctors learn more about how Se-methyl-seleno-L-cysteine works in the body.

Detailed description: PRIMARY OBJECTIVES:

I. To evaluate the toxicity of MSC, given to healthy adult males as a single oral dose.

SECONDARY OBJECTIVES:

I. To characterize the pharmacokinetics of single oral doses of MSC in healthy adult male volunteers.

II. To evaluate the baseline selenium content of toenail clippings in healthy adult males.

OUTLINE: This is a multicenter, randomized, placebo controlled, double blind, dose escalation study. Participants are randomized to 1 of 2 arms.

Arm I: Participants receive oral placebo on day 1.

Arm II: Participants receive oral Se-methyl-seleno-l-cysteine (MSC) on day 1. Cohorts of 5 participants receive escalating doses of MSC until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 5 or 2 of 10 patients experience dose-limiting toxicity.

Participants undergo blood, urine, and toenail clipping collection for pharmacokinetic and correlative studies. Samples are analyzed for plasma protein levels of selenium for proteomic and gene expression, molecular fingerprinting by mass spectrometry, and RNA by gene array analysis.

After completion of study treatment, participants are followed at 7-14 days and at 30 days.

Eligibility criteria: Inclusion Criteria:

* Total body weight between 50 and 115 kg
* Hgb \> 12 gm/dl
* Platelets \> 100,000/μL
* ANC \> 1000/μL
* Creatinine \< 1.5 mg/dl
* SGPT and SGOT \< 3 X the institutional upper limit of normal (ULN)
* Total bilirubin \< 1.5 X the institutional ULN (subjects with a higher level of bilirubin due to a familial metabolism will be considered on an individual basis)
* Life expectancy greater than 2 years
* Male subjects must agree to use adequate contraception (barrier method of birth control; abstinence) prior to study entry and until study completion (i.e., at least two weeks after dose of study drug)
* Ability to understand and the willingness to sign a written informed consent document
* Agree to refrain from use of selenium supplements while on study

Exclusion Criteria:

* Not willing to remain at RPCI, and in follow up, as required
* Presence of medical conditions, which in the opinion of the investigators, would compromise either the subject, or the integrity of the data
* Individuals with a history of active liver or kidney disease within the past 6 months
* Treatment with an investigational drug within 30 days prior to the dose of study drug
* Use of prescription or nonprescription drugs, vitamins, or herbal supplements known to change gastric acidity (e.g., H2-antagonists, proton pump inhibitors, antacids) within 3 days of study drug administration
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to MSC (e.g. reaction to other selenium supplements)
* Subjects who have donated 1 unit of blood within 30 days prior to the first dose of MSC
* Subjects with a known history of heavy metal exposure, such as lead, mercury, of arsenic
* ECOG performance status \> 1
* AUA total symptom score \> 10 (or any individual symptom score of greater than or equal to 4 will exclude the participant)

Primary outcomes:
measure: Clinical toxicity in healthy adult male volunteers, graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v3.0
timeFrame: Up to 30 days
Secondary outcomes:
measure: Characterization of the pharmacokinetics of MSC
timeFrame: Up to 24 hours post-dose
measure: Selenium levels in toenail samples
timeFrame: Up to 24 hours post-dose
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
Study officials:
affiliation: Northwestern University
name: Raymond Bergan
role: PRINCIPAL_INVESTIGATOR
References: