Non-invasive Diagnostics of Iron Deficiency in Surgical Patients by Measuring Zinc Protoporphyrin-IX

• In approx. 40% of the incidences anemia is caused by iron deficiency (= ID). In turn, preoperative iron-deficiency anemia (= IDA) is associated with an increase in morbidity and mortality as well as with the need for a blood transfusion.
• A successful preoperative treatment of IDA via iron supplementation requires a timely screening of iron deficiency, typically done by analyzing specific blood parameters. This however of course requires drawing a blood sample which further reduces the patients' blood volume and is in many cases stated as an inconvenient procedure.
• Measured in blood zinc protoporphyrin-IX (= ZnPP) is an established parameter to detect ID.
• This study aims to evaluate a prototype device detecting ZnPP non-invasively in the intact oral mucosa of surgical patients.
• Results from the non-invasive measurement will be compared to reference measurements of ZnPP from residual blood samples (HPLC analysis) as well as to other parameters including Hb level and iron profile (MCH [= mean corpuscular hemoglobin], MCV [= mean corpuscular volume], ferritin, transferrin, transferrin saturation, soluble transferrin receptor, CRP).

Study Overview

• Status: Completed
• Conditions: Iron-deficiency; Anemia; Iron Deficiency Anemia
• Intervention / Treatment: Diagnostic test: Non-invasive analysis of Zinc protoporphyrin

Detailed Description

The non-invasive measurements will be performed using a prototype device based on fluorescence spectroscopical techniques. In brief, light (restricted wavelengths: 407 / 425nm) will be used to excite ZnPP molecules within the blood of the oral mucosa by means of an optical fibre prob. The outgoing fluorescence emission of the excited molecules will be analyzed using a spectrometer and converted to a ZnPP value [unit: µmol/mol heme] using mathematical transformations as well as spectral fitting.

This study compares the diagnostic performance of iron deficiency based on non-invasive measurements of Zinc protoporphyrin with results based on standard laboratory procedure (i.e. ZnPP measured in whole blood sample using HPLC) and blood values assessed during clinical routine, respectively.

If results of non-invasive and reference measurement techniques yield coinciding results, the non-invasive method could provide an improved mean to detect iron deficiency and thereby to improve treatment of patients suffering from iron deficiency anemia.

• Study Type: Observational
• Enrollment (Actual): 300

Contacts and Locations

Study Locations

• Germany
  • Hesse
    • Frankfurt am Main, Hesse, Germany, 60590
      • Johann Wolfgang Goethe University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

All patients preoperatively screened for anemia in the anemia walk-in clinic of the University Hospital Frankfurt that fit the inclusion criteria will be asked to participate in the study.

Description

Inclusion Criteria:

• Age > 18 years

Exclusion Criteria:

• Patients who received a blood transfusion less than 8 weeks before examination
• Pregnancy

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Study Group; Detecting iron deficiency using various methods. All patients that fit the inclusion criteria and are willing to participate in the study will be included in this group.

Diagnostic test: Non-invasive analysis of Zinc protoporphyrin; In patients fitting the inclusion criteria Zinc protoporphyrin will be measured non-invasively as proxy for iron deficiency. Results will be compared to ZnPP reference values measured via HPLC and with spectroscopical measurements performed on whole blood as well as with blood values (HB, MCH, MCV, ferritin, CRP, transferrin saturation, soluble transferrin receptor) assessed during clinical routine.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Zinc protoporphyrin blood concentration (non-invasive measurement)	Using the prototype device Zinc protoporphyrin blood concentration [unit: µmol/mol heme] will be measured non-invasively in the oral mucosa. Concentrations will be compared (Spearman's Rho, sensitivity, specificity) with Zinc protoporphyrin measurements of whole blood samples (see outcome 2 and 3).	Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Zinc protoporphyrin blood concentration (HPLC reference measurement)	Using HPLC, the analytical reference method, Zinc protoporphyrin blood concentration [unit: µmol/mol heme] will be measured in whole blood samples.	Baseline
Zinc protoporphyrin blood concentration (spectroscopic measurement)	Using fluorescence spectroscopic methods Zinc protoporphyrin blood concentration [unit: µmol/mol heme] will be measured in whole blood samples.	Baseline

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hemoglobin	Hemoglobin levels [unit: g/dL] will be assessed from blood samples using standardized laboratory techniques. Hemoglobin levels will be compared with non-invasive Zinc protoporphyrin measurements (Spearman's Rho, sensitivity, specificity).	Baseline
MCH	MCH (= mean corpuscular hemoglobin) [unit: pg] will be assessed from blood samples using standardized laboratory techniques. MCH will be compared with non-invasive Zinc protoporphyrin measurements (Spearman's Rho, sensitivity, specificity).	Baseline
MCV	MCV (= mean cell volume) [unit: fL = femtoliter] will be assessed from blood samples using standardized laboratory techniques. MCV will be compared with non-invasive Zinc protoporphyrin measurements (Spearman's Rho, sensitivity, specificity).	Baseline
Ferritin	Ferritin [unit: µg/L] will be assessed from blood samples using standardized laboratory techniques. Ferritin levels will be compared with non-invasive Zinc protoporphyrin measurements (Spearman's Rho, sensitivity, specificity).	Baseline
CRP	CRP (= C-reactive protein) [unit: mg/dL] will be assessed from blood samples using standardized laboratory techniques. CRP will be compared with non-invasive Zinc protoporphyrin measurements (Spearman's Rho, sensitivity, specificity).	Baseline
Transferrin saturation	Transferrin saturation [unit: %] will be assessed from blood samples using standardized laboratory techniques. Transferrin saturation will be compared with non-invasive Zinc protoporphyrin measurements (Spearman's Rho, sensitivity, specificity).	Baseline
Soluble transferrin receptor	Soluble Transferrin receptor [unit: mg/L] will be assessed from blood samples using standardized laboratory techniques. Soluble transferrin receptor will be compared with non-invasive Zinc protoporphyrin measurements (Spearman's Rho, sensitivity, specificity).	Baseline

Collaborators and Investigators

• Sponsor: Johann Wolfgang Goethe University Hospital
• Collaborators: Ludwig-Maximilians - University of Munich
• Investigators: Principal Investigator: Patrick Meybohm, Prof. Dr., Johann Wolfgang Goethe University Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 3, 2017
• Primary Completion (ACTUAL): May 1, 2018
• Study Completion (ACTUAL): May 1, 2018

Study Registration Dates

• First Submitted: February 25, 2017
• First Submitted That Met QC Criteria: March 1, 2017
• First Posted (ACTUAL): March 7, 2017

Study Record Updates

• Last Update Posted (ACTUAL): July 17, 2018
• Last Update Submitted That Met QC Criteria: July 14, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: Anemia; Iron-deficiency; Iron-deficiency Anemia; Zinc protoporphyrin
• Additional Relevant MeSH Terms: Metabolic Diseases; Hematologic Diseases; Anemia, Hypochromic; Iron Metabolism Disorders; Anemia, Iron-Deficiency; Anemia; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Photosensitizing Agents; Dermatologic Agents; Protoporphyrin IX; Zinc protoporphyrin
• Other Study ID Numbers: 468/16

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No