Sucrosomal Iron Supplementation in Blood Donors

Iron-deficiency Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04250298
• Other study ID #: 31-435 ex 18/19
• Status: Completed
• Phase: Phase 4
• Start date: November 13, 2019
• Est. completion date: December 20, 2020

Study information

• Verified date: January 2021
• Source: Medical University of Graz
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: December 20, 2020
• Est. primary completion date: September 28, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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);

Related Conditions & MeSH terms

• Anemia, Iron-Deficiency
• Iron-deficiency

Intervention

Dietary Supplement:
• sucrosomal iron
oral intake of iron as sachets or capsules

Locations

Country	Name	City	State
Austria	Medical University of Graz	Graz	Styria

Sponsors (3)

Lead Sponsor	Collaborator
Medical University of Graz	Fresenius Kabi Austria GmbH, Graz, Johannes Kepler University, Linz, Austria

Country where clinical trial is conducted

Austria, 

References & Publications (19)

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. Review. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Murray-Kolb LE, Beard JL. Iron treatment normalizes cognitive functioning in young women. Am J Clin Nutr. 2007 Mar;85(3):778-87. — View Citation

Parisi F, Berti C, Mandò 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. — View Citation

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. — View Citation

Rigas AS, Sørensen CJ, Pedersen OB, Petersen MS, Thørner LW, Kotzé S, Sørensen 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. — View Citation

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. — View Citation

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. — View Citation

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, Pécoud 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. — View Citation

* Note: There are 19 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Hb at E1	Hemoglobin at examination 1 (E1)	day 1
Other	RIS at E1	Symptoms of insomnia at examination 1 (E1)	day 1
Other	RLS at E1	Restless legs syndrome at examination 1 (E1) [yes/no]	day 1
Other	Age at E1	Age at examination 1 (E1) [years]	day 1
Other	Sex	Sex [female/male]	day 1
Other	Body weight	Body weight at examination 1 (E1) [kg]	day 1
Other	Body heights	Body heights at examination 1 (E1) [cm]	day 1
Other	BMI	Body mass index at examination 1 (E1)	day 1
Other	Intake of sucrosomal iron I	sachets or capsules	day 1
Other	Intake number	Number of sachets or capsules (one per day) taken [number]	day 90-120
Other	Intake ratio	Ratio of ingested to prescribed capsules	day 90-120
Other	No intake	days of violation of the intake rules [days]	day 90-120
Other	Diarrhoea	Frequency of diarrhoea during sucrosomal iron intake [days]	90-120 days
Other	Drop out criteria	Drop out criteria [categories]	day 1
Other	Relevant premedication	already discontinued prior medication [categories by type]	day 1
Other	Relevant medication	relevant medication at E1 and during the study [categories by type]	day 1
Other	Relevant pre-existing conditions	relevant already cured pre-existing conditions [categories by type]	day 1
Other	Accompanying diseases	accompanying diseases at at E1 and E1-E2 [categories by type]	day 1
Other	SAE	Serious adverse events [categories by dype and duration]	90-120 days
Other	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
Other	Last menstrual period I	Time interval between the end of the last menstrual period and blood collection for examination 1 [days]	0-90 days
Other	Last menstrual period II	Time interval between the end of the last menstrual period up to examination 2 [days]	90-120 days
Other	Last menstrual period III	Count of menstrual bleedings between blood tests [number]	90-120 days
Primary	Hb at E2 g/dl	hemoglobin level after iron supplementation at examination 2 (E2)	90-120 days
Primary	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
Primary	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
Primary	Hb E1-E2/* Ratio g/dl	Change of hemoglobin ratio of prescribed/taken iron supplementation/ 90 days	90 days
Primary	Delta Response 1	Change of Hb between examination 1 and examination 2 /90 days =1.0 g/dl [yes/no]	90 days
Primary	Delta Response 2	Change of Hb between examination 1 and examination 2 /90 days =1.5 g/dl [yes/no]	90 days
Primary	Response 3	Change of Hb between examination 1 and examination 2 (E2)/90 days =2.0 g/dl [yes/no]	90 days
Primary	Ferritin at E2 (ng/ml)	Ferritin level after iron supplementation at examination 2 (E2)	90-120 days
Primary	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
Primary	Delta Ferritin E1-E2/90 days (ng/ml)	Change of ferritin between examination 1 (E1) to examination 2 (E2)/ 90 days	90 days
Primary	Ferritin E1-E2/Ratio capsule intake 90 days (ng/ml)	Change of ferritin ratio of prescribed/consumed iron supplementation/ 90 days	90 days
Primary	Intake evaluation	Evaluation of the intake of sucrosomal iron [problem-free yes/no]	90-120 days
Primary	Problems with intake	Problems with taking sucrosomal iron [Categories by type]	90-120 days
Primary	Recommendation	Will use of sucrosomal iron for other blood donors be recommended [yes/no]	day 90-120
Primary	Renewed intake	Will sucrosomal iron will be taken again in the given case	day 90-120
Primary	Assumed adverse effects	Assumed test product adverse effects [Categories by type and severity, duration]	90-120 days
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	RLS (E2)	Restless legs syndrome at examination 2 [yes/no]	90-120 days