Effect of Iron on Cerebral Dopamine Receptor Density in Non-anaemic Premenopausal Women With Low Ferritin and Fatigue

Study Overview
=================
Brief Summary
-----------------
This study investigates the effect of intravenous iron substitution in non-anaemic premenopausal women with iron deficiency on: Changes in the cerebral Dopamine (DA) receptor density after iron substitution, shown by brain PET Reduction of fatigue and other neuropsychological symptoms after iron supplementation

Official Title
-----------------
Double-Blind, Single-Center Interventional Trial To Evaluate The Effect Of Intravenous Iron Versus Placebo On Cerebral Dopamine Receptor Density In Non Anaemic Premenopausal Women With Low Ferritin Levels And Fatigue

Conditions
-----------------
Fatigue, Iron-deficiency

Intervention / Treatment
-----------------
* Drug: Iron Carboxymaltose
* Drug: Sodium chloride 0.9%


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy female subjects, Age > 18 years, premenopausal, regularly menstruating BMI 18-25 kg/m2 Serum ferritin level < 15 μg/ml, Hb > 120 g/L Adequate contraception during the study period Fatigue determined as 2 or more points in the basic questionnaire for fatigue Informed consent Exclusion Criteria: Day-night shift work 11 or more points in the BDI No psychiatric disease (as assessed by neuropsychiatric assessment) 15 or more points in the ISI Known hypersensitivity to iron carboxymaltose, iron sucrose or iron sulfate Intake of iron preparations during the last 8 weeks before the start of the trial protocol Pregnancy or lactation Any cardiovascular or pulmonary disease Acute or chronic infection/inflammation or malignancy Other obvious physical or psychiatric causes for fatigue (known mental disorders, e.g. depression) Chronic intake of concurrent medication (especially antipsychotic drugs), except oral contraceptives. Sporadic intake of NSAID or paracetamol, e.g. in the case of a common cold or sporadic headaches is allowed. CRP > 10 mg/L TSH out of normal range Any concurrent medical condition(s) that, in the view of the investigator, would prevent compliance or participation or jeopardize the health of the patients. Participation in any other therapeutic trial within the previous month Known History of HIV/HBV/HCV

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Arm 1<br>Patients will be treated with 0.9% sodium chloride (placebo) at Visit 1 and with iron carboxymaltose in 6 weeks at Visit 2. The patients will be blinded with respect to the treatment sequence. | Drug: Iron Carboxymaltose<br>* Single intravenous infusion within 20 min<br>* Other names: Ferinject®;Drug: Sodium chloride 0.9%<br>* Single intravenous infusion of 250 ml within 20 min<br>* Other names: NaCl 0.9 % (serves as Placebo);|
| Experimental: Treatment Arm 2<br>Patients will be treated with 0.9% sodium chloride (placebo) at Visit 1 and with iron carboxymaltose in 6 weeks at Visit 2. The patients will be blinded with respect to the treatment sequence. | Drug: Iron Carboxymaltose<br>* Single intravenous infusion within 20 min<br>* Other names: Ferinject®;Drug: Sodium chloride 0.9%<br>* Single intravenous infusion of 250 ml within 20 min<br>* Other names: NaCl 0.9 % (serves as Placebo);|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dopamine (DA) receptor density | Changes in the cerebral Dopamine (DA) receptor density determined by brain PET with the 11C-Raclopride tracer | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fatigue | Reduction of fatigue after iron supplementation determined by Fatigue Assessment Scale (FAS) | 6 weeks | 
| Fatigue | Reduction of fatigue after iron supplementation determined by Würzburger Erschöpfungs-Inventar bei Multipler Sklerose (WEIMuS, in German) questionaire | 6 weeks | 
| Neuropsychological symptoms | Reduction of neuropsychological symptoms after iron supplementation determined by neuropsychological assessment | 6 weeks |