Riboflavin as an oral tracer for monitoring compliance in clinical research

V-M Ramanujam, Karl Anderson, James J. Grady, Fatima Nayeem, Leejane Lu

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

We studied urinary riboflavin as an objective biomarker of compliance in clinical research using a simplified method amenable to high throughput analysis. Six healthy women not taking vitamin supplements ingested a study pill containing riboflavin (32 mg) as an inactive tracer and the soy isoflavones daidzin (0.243 mmole) and genistin (0.222 mmole) as active ingredients once daily for four days. Riboflavin and metabolites of the isoflavones were measured in urine samples obtained before and after each pill. Urinary excretion of riboflavin and metabolites of both isoflavones peaked within 8 hrs and remained higher than baseline for 24 hrs. Urinary excretion of riboflavin was also measured in 152 additional women with unrestricted dietary supplement intakes. Mean and median urinary riboflavin concentrations in these women were 0.42 and 0.31 μg/mL, respectively, compared to 0.2 μg/mL during a riboflavin-restricted diet. Receiver operating characteristics (ROC) curves indicated that urinary riboflavin within 24 hrs after a 32 mg dose would perform well as a measure of compliance (all areas under the ROC curves ≥0.84. Samples collected during the initial 8 hrs after pill ingestion performed better as a compliance measure than later collections. In summary, compliance in a clinical study can be monitored in real time by incorporating 32 mg of riboflavin into study pills, with compliance indicated by urinary riboflavin levels increasing over individual baselines or to ≥1.0 μg/mL, with a false positive rate of being classified as compliant at <5%.

Original languageEnglish (US)
Pages (from-to)1-7
Number of pages7
JournalOpen Biomarkers Journal
Volume4
Issue number1
DOIs
StatePublished - 2011

Fingerprint

Riboflavin
Compliance
Monitoring
Research
Isoflavones
Metabolites
ROC Curve
Dietary supplements
Biomarkers
Nutrition
Dietary Supplements
Vitamins
Eating
Throughput
Urine
Diet

Keywords

  • Biomarker
  • Clinical trial
  • Compliance monitoring
  • Riboflavin

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Biochemistry, medical
  • Clinical Biochemistry

Cite this

Riboflavin as an oral tracer for monitoring compliance in clinical research. / Ramanujam, V-M; Anderson, Karl; Grady, James J.; Nayeem, Fatima; Lu, Leejane.

In: Open Biomarkers Journal, Vol. 4, No. 1, 2011, p. 1-7.

Research output: Contribution to journalArticle

@article{dd61d6e940504b0fa2a9bd5469981355,
title = "Riboflavin as an oral tracer for monitoring compliance in clinical research",
abstract = "We studied urinary riboflavin as an objective biomarker of compliance in clinical research using a simplified method amenable to high throughput analysis. Six healthy women not taking vitamin supplements ingested a study pill containing riboflavin (32 mg) as an inactive tracer and the soy isoflavones daidzin (0.243 mmole) and genistin (0.222 mmole) as active ingredients once daily for four days. Riboflavin and metabolites of the isoflavones were measured in urine samples obtained before and after each pill. Urinary excretion of riboflavin and metabolites of both isoflavones peaked within 8 hrs and remained higher than baseline for 24 hrs. Urinary excretion of riboflavin was also measured in 152 additional women with unrestricted dietary supplement intakes. Mean and median urinary riboflavin concentrations in these women were 0.42 and 0.31 μg/mL, respectively, compared to 0.2 μg/mL during a riboflavin-restricted diet. Receiver operating characteristics (ROC) curves indicated that urinary riboflavin within 24 hrs after a 32 mg dose would perform well as a measure of compliance (all areas under the ROC curves ≥0.84. Samples collected during the initial 8 hrs after pill ingestion performed better as a compliance measure than later collections. In summary, compliance in a clinical study can be monitored in real time by incorporating 32 mg of riboflavin into study pills, with compliance indicated by urinary riboflavin levels increasing over individual baselines or to ≥1.0 μg/mL, with a false positive rate of being classified as compliant at <5{\%}.",
keywords = "Biomarker, Clinical trial, Compliance monitoring, Riboflavin",
author = "V-M Ramanujam and Karl Anderson and Grady, {James J.} and Fatima Nayeem and Leejane Lu",
year = "2011",
doi = "10.2174/1875318301104010001",
language = "English (US)",
volume = "4",
pages = "1--7",
journal = "Open Biomarkers Journal",
issn = "1875-3183",
publisher = "Bentham Science Publishers B.V.",
number = "1",

}

TY - JOUR

T1 - Riboflavin as an oral tracer for monitoring compliance in clinical research

AU - Ramanujam, V-M

AU - Anderson, Karl

AU - Grady, James J.

AU - Nayeem, Fatima

AU - Lu, Leejane

PY - 2011

Y1 - 2011

N2 - We studied urinary riboflavin as an objective biomarker of compliance in clinical research using a simplified method amenable to high throughput analysis. Six healthy women not taking vitamin supplements ingested a study pill containing riboflavin (32 mg) as an inactive tracer and the soy isoflavones daidzin (0.243 mmole) and genistin (0.222 mmole) as active ingredients once daily for four days. Riboflavin and metabolites of the isoflavones were measured in urine samples obtained before and after each pill. Urinary excretion of riboflavin and metabolites of both isoflavones peaked within 8 hrs and remained higher than baseline for 24 hrs. Urinary excretion of riboflavin was also measured in 152 additional women with unrestricted dietary supplement intakes. Mean and median urinary riboflavin concentrations in these women were 0.42 and 0.31 μg/mL, respectively, compared to 0.2 μg/mL during a riboflavin-restricted diet. Receiver operating characteristics (ROC) curves indicated that urinary riboflavin within 24 hrs after a 32 mg dose would perform well as a measure of compliance (all areas under the ROC curves ≥0.84. Samples collected during the initial 8 hrs after pill ingestion performed better as a compliance measure than later collections. In summary, compliance in a clinical study can be monitored in real time by incorporating 32 mg of riboflavin into study pills, with compliance indicated by urinary riboflavin levels increasing over individual baselines or to ≥1.0 μg/mL, with a false positive rate of being classified as compliant at <5%.

AB - We studied urinary riboflavin as an objective biomarker of compliance in clinical research using a simplified method amenable to high throughput analysis. Six healthy women not taking vitamin supplements ingested a study pill containing riboflavin (32 mg) as an inactive tracer and the soy isoflavones daidzin (0.243 mmole) and genistin (0.222 mmole) as active ingredients once daily for four days. Riboflavin and metabolites of the isoflavones were measured in urine samples obtained before and after each pill. Urinary excretion of riboflavin and metabolites of both isoflavones peaked within 8 hrs and remained higher than baseline for 24 hrs. Urinary excretion of riboflavin was also measured in 152 additional women with unrestricted dietary supplement intakes. Mean and median urinary riboflavin concentrations in these women were 0.42 and 0.31 μg/mL, respectively, compared to 0.2 μg/mL during a riboflavin-restricted diet. Receiver operating characteristics (ROC) curves indicated that urinary riboflavin within 24 hrs after a 32 mg dose would perform well as a measure of compliance (all areas under the ROC curves ≥0.84. Samples collected during the initial 8 hrs after pill ingestion performed better as a compliance measure than later collections. In summary, compliance in a clinical study can be monitored in real time by incorporating 32 mg of riboflavin into study pills, with compliance indicated by urinary riboflavin levels increasing over individual baselines or to ≥1.0 μg/mL, with a false positive rate of being classified as compliant at <5%.

KW - Biomarker

KW - Clinical trial

KW - Compliance monitoring

KW - Riboflavin

UR - http://www.scopus.com/inward/record.url?scp=80053483548&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80053483548&partnerID=8YFLogxK

U2 - 10.2174/1875318301104010001

DO - 10.2174/1875318301104010001

M3 - Article

VL - 4

SP - 1

EP - 7

JO - Open Biomarkers Journal

JF - Open Biomarkers Journal

SN - 1875-3183

IS - 1

ER -