Sucrosomal Iron Supplementation in Blood Donors

Pilot Study to Gain First Indications for the Impact of a Three-month's Oral Intake of an Iron Supplement With High Bioavailability on the Hemoglobin Concentration in Iron Deficient Blood Donors

The aim of this descriptive/explorative pilot study is to examine the effects of supplementing a sucrosomal iron preparation in whole blood donors with iron deficiency for three months.

Study Overview

• Status: Completed
• Conditions: Iron-deficiency
• Intervention / Treatment: Dietary supplement: sucrosomal iron

Detailed Description

In this academic, monocentric interventional pilot study with one cohorte, otherwise healthy blood donors who have been rejected from blood donation due to low hemoglobin (females <12.5 g/dl, males <13.5 g/dl) and low ferritin levels (<30 ng/ml) receive an iron-containing dietary supplement (sucrosomal iron) for three months with a daily intake of 30 g iron.

Fifty donors will be included in the study. The study population will consist of two sub-groups (premenopausal women and postmenopausal women plus men).

Our aim is to

• gain first findings concerning the extent of the change primarily in hemoglobin and secondly in ferritin concentrations
• observe acceptance and tolerance after intake of the test product for several months
• create pilot data for a following randomized controlled study.

In addition, possible clinical symptoms associated with iron deficiency will be recorded by using appropriate questionnaires (Questionnaire on the assessment of health-related quality of life [WHOQOL-Bref], Fatigue questionnaire [FAQ], questionnaire on psychic symptoms of insomnia [RIS] and Restless Legs Syndrome).

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 4

Contacts and Locations

Study Locations

• Austria
  • Styria
    • Graz, Styria, Austria, 8036
      • Medical University of Graz

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Deferral from donation because of low capillary hemoglobin (Hb) <12.5 g/dl (women) and Hb <13 g/dl;
• Otherwise eligibility for donation according to medical history;
• Ferritin at the time of deferral <30 ng/ml;
• Last whole blood donation >2 months prior to current hemoglobin level;
• Written informed consent;
• Venous Hb <12.5 g/dl (females) and <13.5 g/dl (men);

Exclusion Criteria:

• Lack of legal capacity or court-appointed representation;
• Known pregnancy;
• Lactation period;
• Chronic diarrhea or known inclination for diarrhea;
• Known or suspected fructose intolerance;
• iron supplementation during the last three months;
• continuous or expected blood loss (capillary oozing);
• hypermenorrhea;
• planned surgical intervention with relevant blood loss within the next 3-4 months (duration of study);
• application of another iron supplementation during the next 3-4 months;
• intended application of preparations for a systematic increase of red blood cell and hemoglobin concentration or production (e.g. erythropoietin preparations, packed red blood cells) for the duration of the study;
• parallel participation in another clinical trial with insurance coverage;
• foreseeable compliance issues;
• foreseeable unavailability for the time of the final examination;
• Incompatibility with any of the ingredients of the product;
• Anemia requiring acute therapy: Hb <8g/dl (as indication of an obligatory correction of the hemoglobin level to a clinically irrelevant or non-therapeutic value);

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Iron deficient blood donors; Daily intake of 30 mg of sucrosomal iron during 90-120 days (male and female whole blood donors)	Dietary supplement: sucrosomal iron; oral intake of iron as sachets or capsules; Other Names: OLEOvital(R) EISEN FORTE

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hb at E2 g/dl	hemoglobin level after iron supplementation at examination 2 (E2)	90-120 days
Delta Hb E1-E2 g/dl	Change of hemoglobin between visit 1 (E1) prior to iron substitution and examination 2 (E2) after iron substitution	90-120 days
Hb E1-E2/90 days g/dl	Change of hemoglobin between examination 1 (E1) prior to iron substitution and examination 2 (E2) after iron substitution/90 days	90 days
Hb E1-E2/* Ratio g/dl	Change of hemoglobin ratio of prescribed/taken iron supplementation/ 90 days	90 days
Delta Response 1	Change of Hb between examination 1 and examination 2 /90 days ≥1.0 g/dl [yes/no]	90 days
Delta Response 2	Change of Hb between examination 1 and examination 2 /90 days ≥1.5 g/dl [yes/no]	90 days
Response 3	Change of Hb between examination 1 and examination 2 (E2)/90 days ≥2.0 g/dl [yes/no]	90 days
Ferritin at E2 (ng/ml)	Ferritin level after iron supplementation at examination 2 (E2)	90-120 days
Delta Ferritin E1-E2 (ng/ml)	Change of Hemoglobin between examination 1 (E1) prior to iron substitution and examination 2 (E2) after iron substitution	90-120 days
Delta Ferritin E1-E2/90 days (ng/ml)	Change of ferritin between examination 1 (E1) to examination 2 (E2)/ 90 days	90 days
Ferritin E1-E2/Ratio capsule intake 90 days (ng/ml)	Change of ferritin ratio of prescribed/consumed iron supplementation/ 90 days	90 days
Intake evaluation	Evaluation of the intake of sucrosomal iron [problem-free yes/no]	90-120 days
Problems with intake	Problems with taking sucrosomal iron [Categories by type]	90-120 days
Recommendation	Will use of sucrosomal iron for other blood donors be recommended [yes/no]	day 90-120
Renewed intake	Will sucrosomal iron will be taken again in the given case	day 90-120
Assumed adverse effects	Assumed test product adverse effects [Categories by type and severity, duration]	90-120 days
Clinical symptoms of iron deficiency	Items of the questionnaire for basic on possible clinical symptoms of iron deficiency and for the evaluation of sucrosomal iron [narrative, categories]	90-120 days
WHOQOL-Bref (E2)	The WHO Quality of Life Assessment (abbreviated) includes 16 items with values of 1-5 (negatively phrased items are reversed for analysis.) Higher scores denote a higher quality of life.	14 days
Delta WHOQOL-Bref (E1-E2)	The WHO Quality of Life Assessment includes 16 items with values of 1-5. Higher scores denote a higher quality of life. In this outcome changes in quality of life are assessed by determining the differences between examination 1 and examination 2.	14 days
FAQ (E2)	In the Fatigue Assessment Questionnaire fatigue at examination 2 will be determined. Values range from 0-3, including 23 items. The higher the score is the worse is the outcome.	7 days
Delta FAQ (E1-E2)	In the Fatigue Assessment Questionnaire fatigue will be determined at E1 and E2. Values range from 0-3. In this outcome the change of fatigue between examination 1 and examination 2 will be determined.	7 days
RIS at E2	Symptoms of insomnia (Regensburg Insomnia Scale) will be determined at examination 2. The questionnaire consists of 10 items with values of 0-4. Higher scores denote a worse outcome.	28 days
Change RIS (E1-E2)	Change of symptoms of insomnia between examination 1 and examination 2. Symptoms of insomnia (Regensburg Insomnia Scale) will be determined at examination 1 and 2. In this outcome the difference between E1 and E2 will be determined. The questionnaire consists of 10 items with values of 0-4. Higher scores denote a worse outcome.	28 days
RLS (E2)	Restless legs syndrome at examination 2 [yes/no]	90-120 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hb at E1	Hemoglobin at examination 1 (E1)	day 1
RIS at E1	Symptoms of insomnia at examination 1 (E1)	day 1
RLS at E1	Restless legs syndrome at examination 1 (E1) [yes/no]	day 1
Age at E1	Age at examination 1 (E1) [years]	day 1
Sex	Sex [female/male]	day 1
Body weight	Body weight at examination 1 (E1) [kg]	day 1
Body heights	Body heights at examination 1 (E1) [cm]	day 1
BMI	Body mass index at examination 1 (E1)	day 1
Intake of sucrosomal iron I	sachets or capsules	day 1
Intake number	Number of sachets or capsules (one per day) taken [number]	day 90-120
Intake ratio	Ratio of ingested to prescribed capsules	day 90-120
No intake	days of violation of the intake rules [days]	day 90-120
Diarrhoea	Frequency of diarrhoea during sucrosomal iron intake [days]	90-120 days
Drop out criteria	Drop out criteria [categories]	day 1
Relevant premedication	already discontinued prior medication [categories by type]	day 1
Relevant medication	relevant medication at E1 and during the study [categories by type]	day 1
Relevant pre-existing conditions	relevant already cured pre-existing conditions [categories by type]	day 1
Accompanying diseases	accompanying diseases at at E1 and E1-E2 [categories by type]	day 1
SAE	Serious adverse events [categories by dype and duration]	90-120 days
Time intervals	Time intervals between examination 1 and 2, 1st blood sample and examination 1 and 1st blood sample and V2 [days]	90-120 days
Last menstrual period I	Time interval between the end of the last menstrual period and blood collection for examination 1 [days]	0-90 days
Last menstrual period II	Time interval between the end of the last menstrual period up to examination 2 [days]	90-120 days
Last menstrual period III	Count of menstrual bleedings between blood tests [number]	90-120 days

Collaborators and Investigators

• Sponsor: Medical University of Graz
• Collaborators: Johannes Kepler University of Linz; Fresenius Kabi Austria GmbH, Graz

Publications and helpful links

General Publications

• Bianco C, Brittenham G, Gilcher RO, Gordeuk VR, Kushner JP, Sayers M, Chambers L, Counts RB, Aylesworth C, Nemo G, Alving B. Maintaining iron balance in women blood donors of childbearing age: summary of a workshop. Transfusion. 2002 Jun;42(6):798-805. doi: 10.1046/j.1537-2995.2002.00103.x. No abstract available.
• Verdon F, Burnand B, Stubi CL, Bonard C, Graff M, Michaud A, Bischoff T, de Vevey M, Studer JP, Herzig L, Chapuis C, Tissot J, Pecoud A, Favrat B. Iron supplementation for unexplained fatigue in non-anaemic women: double blind randomised placebo controlled trial. BMJ. 2003 May 24;326(7399):1124. doi: 10.1136/bmj.326.7399.1124.
• Bialkowski W, Bryant BJ, Schlumpf KS, Wright DJ, Birch R, Kiss JE, D'Andrea P, Cable RG, Spencer BR, Vij V, Mast AE. The strategies to reduce iron deficiency in blood donors randomized trial: design, enrolment and early retention. Vox Sang. 2015 Feb;108(2):178-85. doi: 10.1111/vox.12210. Epub 2014 Dec 3.
• Finch CA, Cook JD, Labbe RF, Culala M. Effect of blood donation on iron stores as evaluated by serum ferritin. Blood. 1977 Sep;50(3):441-7.
• Cable RG, Glynn SA, Kiss JE, Mast AE, Steele WR, Murphy EL, Wright DJ, Sacher RA, Gottschall JL, Vij V, Simon TL; NHLBI Retrovirus Epidemiology Donor Study-II. Iron deficiency in blood donors: analysis of enrollment data from the REDS-II Donor Iron Status Evaluation (RISE) study. Transfusion. 2011 Mar;51(3):511-22. doi: 10.1111/j.1537-2995.2010.02865.x. Epub 2010 Aug 30.
• Rigas AS, Sorensen CJ, Pedersen OB, Petersen MS, Thorner LW, Kotze S, Sorensen E, Magnussen K, Rostgaard K, Erikstrup C, Ullum H. Predictors of iron levels in 14,737 Danish blood donors: results from the Danish Blood Donor Study. Transfusion. 2014 Mar;54(3 Pt 2):789-96. doi: 10.1111/trf.12518. Epub 2013 Dec 23.
• Conrad ME, Crosby WH, Jacobs A, Kaltwasser JP, Nusbacher J. The Hippocratian principle of 'primum nil nocere' demands that the metabolic state of a donor should be normalized prior to a subsequent donation of blood or plasma. How much blood, relative to his body weight, can a donor give over a certain period, without a continuous deviation of iron metabolism in the direction of iron deficiency? Vox Sang. 1981 Nov-Dec;41(5-6):336-43. doi: 10.1111/j.1423-0410.1981.tb01059.x. No abstract available.
• Cable RG, Brambilla D, Glynn SA, Kleinman S, Mast AE, Spencer BR, Stone M, Kiss JE; National Heart, Lung, and Blood Institute Recipient Epidemiology and Donor Evaluation Study-III (REDS-III). Effect of iron supplementation on iron stores and total body iron after whole blood donation. Transfusion. 2016 Aug;56(8):2005-12. doi: 10.1111/trf.13659. Epub 2016 May 27.
• Kiss JE, Brambilla D, Glynn SA, Mast AE, Spencer BR, Stone M, Kleinman SH, Cable RG; National Heart, Lung, and Blood Institute (NHLBI) Recipient Epidemiology and Donor Evaluation Study-III (REDS-III). Oral iron supplementation after blood donation: a randomized clinical trial. JAMA. 2015 Feb 10;313(6):575-83. doi: 10.1001/jama.2015.119.
• Moretti D, Goede JS, Zeder C, Jiskra M, Chatzinakou V, Tjalsma H, Melse-Boonstra A, Brittenham G, Swinkels DW, Zimmermann MB. Oral iron supplements increase hepcidin and decrease iron absorption from daily or twice-daily doses in iron-depleted young women. Blood. 2015 Oct 22;126(17):1981-9. doi: 10.1182/blood-2015-05-642223. Epub 2015 Aug 19.
• Stoffel NU, Cercamondi CI, Brittenham G, Zeder C, Geurts-Moespot AJ, Swinkels DW, Moretti D, Zimmermann MB. Iron absorption from oral iron supplements given on consecutive versus alternate days and as single morning doses versus twice-daily split dosing in iron-depleted women: two open-label, randomised controlled trials. Lancet Haematol. 2017 Nov;4(11):e524-e533. doi: 10.1016/S2352-3026(17)30182-5. Epub 2017 Oct 9.
• Pisani A, Riccio E, Sabbatini M, Andreucci M, Del Rio A, Visciano B. Effect of oral liposomal iron versus intravenous iron for treatment of iron deficiency anaemia in CKD patients: a randomized trial. Nephrol Dial Transplant. 2015 Apr;30(4):645-52. doi: 10.1093/ndt/gfu357. Epub 2014 Nov 13.
• Parisi F, Berti C, Mando C, Martinelli A, Mazzali C, Cetin I. Effects of different regimens of iron prophylaxis on maternal iron status and pregnancy outcome: a randomized control trial. J Matern Fetal Neonatal Med. 2017 Aug;30(15):1787-1792. doi: 10.1080/14767058.2016.1224841. Epub 2016 Sep 2.
• Spencer BR, Kleinman S, Wright DJ, Glynn SA, Rye DB, Kiss JE, Mast AE, Cable RG; REDS-II RISE Analysis Group. Restless legs syndrome, pica, and iron status in blood donors. Transfusion. 2013 Aug;53(8):1645-52. doi: 10.1111/trf.12260. Epub 2013 Jun 13.
• Brownlie T 4th, Utermohlen V, Hinton PS, Haas JD. Tissue iron deficiency without anemia impairs adaptation in endurance capacity after aerobic training in previously untrained women. Am J Clin Nutr. 2004 Mar;79(3):437-43. doi: 10.1093/ajcn/79.3.437.
• Murray-Kolb LE, Beard JL. Iron treatment normalizes cognitive functioning in young women. Am J Clin Nutr. 2007 Mar;85(3):778-87. doi: 10.1093/ajcn/85.3.778.
• Moeinvaziri M, Mansoori P, Holakooee K, Safaee Naraghi Z, Abbasi A. Iron status in diffuse telogen hair loss among women. Acta Dermatovenerol Croat. 2009;17(4):279-84.
• Chansky MC, King MR, Bialkowski W, Bryant BJ, Kiss JE, D'Andrea P, Cable RG, Spencer BR, Mast AE. Qualitative assessment of pica experienced by frequent blood donors. Transfusion. 2017 Apr;57(4):946-951. doi: 10.1111/trf.13981. Epub 2017 Feb 5.
• Allen RP, Picchietti D, Hening WA, Trenkwalder C, Walters AS, Montplaisi J; Restless Legs Syndrome Diagnosis and Epidemiology workshop at the National Institutes of Health; International Restless Legs Syndrome Study Group. Restless legs syndrome: diagnostic criteria, special considerations, and epidemiology. A report from the restless legs syndrome diagnosis and epidemiology workshop at the National Institutes of Health. Sleep Med. 2003 Mar;4(2):101-19. doi: 10.1016/s1389-9457(03)00010-8.

Study record dates

Study Major Dates

• Study Start (Actual): November 13, 2019
• Primary Completion (Actual): September 28, 2020
• Study Completion (Actual): December 20, 2020

Study Registration Dates

• First Submitted: January 21, 2020
• First Submitted That Met QC Criteria: January 30, 2020
• First Posted (Actual): January 31, 2020

Study Record Updates

• Last Update Posted (Actual): January 22, 2021
• Last Update Submitted That Met QC Criteria: January 21, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: dietary supplements; blood donors; donor rejection; sucrosomal iron
• Additional Relevant MeSH Terms: Metabolic Diseases; Hematologic Diseases; Anemia, Hypochromic; Anemia; Iron Metabolism Disorders; Anemia, Iron-Deficiency
• Other Study ID Numbers: 31-435 ex 18/19

Drug and device information, study documents

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