Fatigue, Iron Deficiency
Conditions
Keywords
Fatigue, Blood donation, Iron deficiency, Ferrous sulphate, Donation, Donors, Iron, Ferritin, Hemoglobin, Anemia, Anaemia, Haemoglobin, Don, Women blood donors
Brief summary
The purpose of this study is to determine the subjective response of iron substitution (Tardyferon®) on fatigue in women blood donors with a mean serum ferritin \< 30ng/ml and to assess variation of ferritin and hemoglobin after a blood donation.
Detailed description
* Actually, there's no recommendation to check ferritin level in blood donors, even if several studies pointed out the high prevalence of iron deficiency after a blood donation. Furthermore, some clinical trials showed that non-anaemic women with unexplained fatigue may benefit from iron supplementation. * The purpose of this study is to determine the subjective response of iron substitution (Tardyferon®) on fatigue in women blood donors with a mean serum ferritin \< 30ng/ml and to assess variation of ferritin and hemoglobin after a blood donation. * We will measure blood count, ferritin level and C-reactive protein at the time of the blood donation and then after a week, a month and 3 months. A week after the blood donation, donors with a ferritin level \<30 ng/ml and hemoglobin \> 120g/l (non anaemic) will be included in the study and randomised. A one-month iron treatment vs placebo will be introduced. To assess the subjective response on fatigue, the donors will fill in different questionnaires at the time of the blood donation and then after a week, a month and 3 months.
Interventions
DRUGFerrous sulphate
Volunteers will receive 80 mg/day oral ferrous sulphate (Tardyferon®) for four weeks. Visual analogical scales and questionnaires will be performed at day 0 and 30 to quantify fatigue ( Fatigue Severity Scale). We will also check depression and anxiety symptoms ( Prime MD ) and health survey ( SF-12 ). An evaluation of the menstruation ( Pictorial Bleeding Assessment Chart of Jansen) will be performed at day 0 to detect a possible hypermenorrhea (appendix 1-4). A physical test will be performed (Chester Step Test) to assess the VO2 max. Every side effect will be written on follow-up notes.
DRUGPlacebo
Volunteers will receive 1 pill/day oral placebo for four weeks. Visual analogical scales and questionnaires will be performed at day 0 and 30 to quantify fatigue ( Fatigue Severity Scale). We will also check depression and anxiety symptoms ( Prime MD ) and health survey ( SF-12 ). An evaluation of the menstruation ( Pictorial Bleeding Assessment Chart of Jansen) will be performed at day 0 to detect a possible hypermenorrhea (appendix 1-4). A physical test will be performed (Chester Step Test) to assess the VO2 max. Every side effect will be written on follow-up notes.
Sponsors
Pierre Fabre Laboratories
University of Lausanne
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* women * aged 18 - 50 * eligible for a blood donation
Exclusion criteria
* men * age below 18 or above 50 * not eligible for a blood donation (according to the blood donation eligibility guidelines of the Swiss Red Cross) * hemochromatosis, psychiatric / thyroid / hepatic / rheumatismal / kidney or cardiopulmonary diseases that can cause fatigue * intestinal disease or medical treatment that can perturb iron absorption and/or excretion * donors with mental disorder or psychiatric disease that are unable to give consent * acute or chronic inflammation * diabetes and pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Level of Fatigue Before and After Iron Treatment/Placebo, Using a 10 Point Visual Analogue Scale. | baseline and 4 weeks | The level of fatigue perceived at baseline and after 4 weeks was scored on a 10-point visual analogue scale ranging from no fatigue=0 to very severe fatigue=10. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hemoglobin Variation Before and After Treatment vs Placebo | baseline and 4 weeks | The level of hemoglobin measured 4 weeks after randomization |
| Ferritin Change Before and After 4 Weeks of Treatment/Placebo | baseline and 4 weeks | Level of ferritin measured 4 weeks after randomization |
| Aerobic Capacity Using an Indirect Measurement of VO2Max : Chester Step Test | baseline and 4 weeks | Subjects were asked to step on to and off a 20cm step at a rate set by a metronome. Step rate increased gradually until subject reached her submaximal predicted heart rate. |
| Response of Iron Supplementation on Mental Disorder | baseline and 4 weeks | Depression was assessed using the Prime-MD Patient Health Questionnaire (PHQ-9), self-administered by the subject.Diagnosis of depression syndrom was made scoring results of the nine item (range : 0-3). A score \>15 (range of total overall scale:0-27) was considered as a depression syndrome. The outcome measure is the number the donors with a depression syndrome at baseline who had a positive response (total score= or \<15) after placebo or treatment. |
| Adherence to Treatment. | 4 weeks | Adherence to treatment was calculated as the number of days with at least one opening of the electronic device divided by the total number of monitored days. The device was a MEMS (Medication Event Monitoring System,AARDEX, Europe, Switzerland) |
Countries
Switzerland
Participant flow
Recruitment details
Premopausal female blood donors coming spontaneously to the donation center, were asked to participated to this study. After agreement an informed consent was signed.
Pre-assignment details
One week after whole blood donation, participants were randomized if they were not anemic and their ferritin level was \< or = 30 ng/mL.
Participants by arm
| Arm | Count |
|---|---|
| Oral Treatment of Iron One week after donation, donors self-administered ferrous sulfate (80mg of elemental iron daily) during one month. | 78 |
| Placebo One week after donation, donors self-administered on pill of placebo (daily), during one month. | 76 |
| Total | 154 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 4 | 5 |
Baseline characteristics
| Characteristic | Placebo | Oral Treatment of Iron | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 76 Participants | 78 Participants | 154 Participants |
| Age Continuous | 30.7 years STANDARD_DEVIATION 8.8 | 32.9 years STANDARD_DEVIATION 8.4 | 31.6 years STANDARD_DEVIATION 8.7 |
| Region of Enrollment Switzerland | 76 participants | 78 participants | 154 participants |
| Sex: Female, Male Female | 76 Participants | 78 Participants | 154 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 29 / 74 | 11 / 71 |
| serious Total, serious adverse events | 0 / 74 | 0 / 71 |
Outcome results
Primary
Level of Fatigue Before and After Iron Treatment/Placebo, Using a 10 Point Visual Analogue Scale.
The level of fatigue perceived at baseline and after 4 weeks was scored on a 10-point visual analogue scale ranging from no fatigue=0 to very severe fatigue=10.
Time frame: baseline and 4 weeks
Population: The sample size for randomized volunteers was calculated using a two-sample comparison of means to detect a one point difference in the visual analogical scale (first outcome).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oral Treatment of Iron | Level of Fatigue Before and After Iron Treatment/Placebo, Using a 10 Point Visual Analogue Scale. | 3.4 centimeter | Standard Deviation 2.4 |
| Placebo | Level of Fatigue Before and After Iron Treatment/Placebo, Using a 10 Point Visual Analogue Scale. | 3.5 centimeter | Standard Deviation 2.5 |
Comparison: The null hypothesis was that there was no difference in fatigue VAS scores between the treatment and placebo groups at 4 weeksp-value: 0.6995% CI: [0, 10]Regression, Linear
Secondary
Adherence to Treatment.
Adherence to treatment was calculated as the number of days with at least one opening of the electronic device divided by the total number of monitored days. The device was a MEMS (Medication Event Monitoring System,AARDEX, Europe, Switzerland)
Time frame: 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oral Treatment of Iron | Adherence to Treatment. | 96 percentage of day | Standard Deviation 16.7 |
| Placebo | Adherence to Treatment. | 96 percentage of day | Standard Deviation 14.2 |
Secondary
Aerobic Capacity Using an Indirect Measurement of VO2Max : Chester Step Test
Subjects were asked to step on to and off a 20cm step at a rate set by a metronome. Step rate increased gradually until subject reached her submaximal predicted heart rate.
Time frame: baseline and 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oral Treatment of Iron | Aerobic Capacity Using an Indirect Measurement of VO2Max : Chester Step Test | 40.5 mLO2/kg/min | Standard Deviation 14.5 |
| Placebo | Aerobic Capacity Using an Indirect Measurement of VO2Max : Chester Step Test | 40.1 mLO2/kg/min | Standard Deviation 17 |
p-value: 0.0595% CI: [0, 6]Regression, Linear
Secondary
Ferritin Change Before and After 4 Weeks of Treatment/Placebo
Level of ferritin measured 4 weeks after randomization
Time frame: baseline and 4 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oral Treatment of Iron | Ferritin Change Before and After 4 Weeks of Treatment/Placebo | 28.0 ng/mL | Standard Deviation 9.8 |
| Placebo | Ferritin Change Before and After 4 Weeks of Treatment/Placebo | 12.9 ng/mL | Standard Deviation 8.3 |
p-value: <0.0595% CI: [0, 30]Regression, Linear
Secondary
Hemoglobin Variation Before and After Treatment vs Placebo
The level of hemoglobin measured 4 weeks after randomization
Time frame: baseline and 4 weeks
Population: The number of participants was calculated according to the primary outcome.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oral Treatment of Iron | Hemoglobin Variation Before and After Treatment vs Placebo | 135 g/L | Standard Deviation 6.7 |
| Placebo | Hemoglobin Variation Before and After Treatment vs Placebo | 130 g/L | Standard Deviation 5.3 |
p-value: <0.0595% CI: [0, 10]Regression, Linear
Secondary
Response of Iron Supplementation on Mental Disorder
Depression was assessed using the Prime-MD Patient Health Questionnaire (PHQ-9), self-administered by the subject.Diagnosis of depression syndrom was made scoring results of the nine item (range : 0-3). A score \>15 (range of total overall scale:0-27) was considered as a depression syndrome. The outcome measure is the number the donors with a depression syndrome at baseline who had a positive response (total score= or \<15) after placebo or treatment.
Time frame: baseline and 4 weeks
Population: Number of participant was set according the primary outcome.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Oral Treatment of Iron | Response of Iron Supplementation on Mental Disorder | 3 participants |
| Placebo | Response of Iron Supplementation on Mental Disorder | 4 participants |