Back to resultsEstrogen Replacement in Anorexia Nervosa (HOSAN)
Primary Purpose
Anorexia Nervosa
Status
Terminated
Phase
Phase 2
Locations
Germany
Study Type
Interventional
Intervention
ethinyl estradiol 0.03mg and dienogest 2 mg (combination)
Placebo oral capsule
Sponsored by
About this trial
This is an interventional treatment trial for Anorexia Nervosa focused on measuring anorexia nervosa, estrogen, psychotherapy, cortisol, appetite regulation, neurocognitive performance, eating disorder, sexual hormone
Eligibility Criteria
Inclusion Criteria:
- anorexia nervosa according to the Diagnostic and Statistical Manual of Mental Disorders (DSM V) or subsyndromal anorexia nervosa (lack of a diagnostic symptom according to DSM V)
- BMI ≥ 13 kg/m2 and ≤ 18.5 kg/m2
- able to provide written informed consent
Exclusion Criteria:
- a known hypersensitivity to the active compound or to other components of the study drug
- one or more contraindications for the use of hormonal contraception: Smoking over 20 cigarettes/day; Acute venous thromboembolic disease or increased risk; Known hereditary or acquired predisposition for venous thrombosis, e.g. activated protein C (APC)-resistance (including factor V Leiden Mutation), antithrombin III deficiency, protein C deficiency, protein S deficiency; Risk for arterial thromboembolism (diabetes mellitus with vascular sequelae, severe hypertonus, severe dyslipoproteinemia); Known hereditary or acquired predisposition for arterial thrombosis, e.g. hyperhomocysteinemia and anti-phospholipid antibodies (anticardiolipin antibodies, Lupus anticoagulants); Cerebrovascular disease (past cerebral infarction or prodromal states such as transitory ischemia attacks); Past migraine with focal neurological symptoms; Liver disease or pancreatitis; Dubin-Johnson syndrome and Rotor syndrome; Known porphyria; Known or suspected sexual hormone sensitive tumors; Unresolved vaginal bleeding
- a present severe depressive episode (major depression) according to the DSM V
- past or present alcohol or drug abuse
- severe psychiatric disorders (axis I) according to the DSM V (such as bipolar affective disorder or schizophrenia) in addition to anorexia nervosa
- suicidality
- known diabetes mellitus
- severe somatic comorbidity or organ dysfunction that is not compatible with intake of the study drug
- use of hormonal depot compounds (injectable drugs, implants), or hormonal intrauterine pessaries during the last four weeks before the screening visit (V1)
- pregnancy
- breastfeeding during the last 6 months before V1
Sites / Locations
- Department of Psychosomatic Medicine and Psychotherapy, University Hospital Erlangen
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
verum group
placebo group
Arm Description
approved oral contraceptive: ethinyl estradiol 0.03mg and dienogest 2mg (combination drug) daily intake over 10 weeks
placebo
Outcomes
Primary Outcome Measures
Changes in neurocognitive performance
Performance based on a neurocognitive test battery
Secondary Outcome Measures
Incidence of treatment-emergent adverse Events (AE) (safety/tolerability)
Number of adverse events (including AE, AR, severe AE, SAR and SUSAR)
Changes in psychopathology (EDE-Q)
Changes in sum scores in the EDE-Q
Changes in psychopathology (EDI-2)
Changes in sum scores in the EDI-2
Changes in psychopathology (STAI)
Changes in sum scores in the STAI
Changes in psychopathology (Patient Health Questionnaire-9, PHQ-9)
Changes in sum scores in the PHQ-9
Changes in psychopathology (Eating Disorder Quality of Life, EDQoL)
Changes in sum scores in the EDQoL
Neuroendocrinological changes (cortisol)
Changes in plasma cortisol levels during a dexamethasone suppression test
Neuroendocrinological changes (glucose)
Changes in plasma concentrations of glucose
Neuroendocrinological changes (insulin)
Changes in plasma concentrations of insulin
Neuroendocrinological changes (ghrelin)
Changes in plasma concentrations of the appetite-regulating peptide ghrelin
Neuroendocrinological changes (leptin)
Changes in plasma concentrations of the appetite-regulating peptide leptin
Changes in antidepressant medication
Changes in antidepressants´ use
Full Information
NCT ID
NCT03172533
First Posted
May 22, 2017
Last Updated
January 28, 2019
Sponsor
University of Erlangen-Nürnberg Medical School
1. Study Identification
Unique Protocol Identification Number
NCT03172533
Brief Title
Estrogen Replacement in Anorexia Nervosa
Acronym
HOSAN
Official Title
Prospective, Randomized, Double-blind, Placebo-controlled Clinical Trial on the Effects of an Estrogen-progestin Combination as add-on to Inpatient Psychotherapy in Adult Female Patients Suffering From Anorexia Nervosa
Study Type
Interventional
2. Study Status
Record Verification Date
January 2019
Overall Recruitment Status
Terminated
Why Stopped
Difficulties in recruitment
Study Start Date
March 15, 2016 (Actual)
Primary Completion Date
January 15, 2019 (Actual)
Study Completion Date
January 15, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Erlangen-Nürnberg Medical School
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
The present study is a placebo-controlled randomised study on the effects of estrogen replacement upon AN-associated psychopathology, several neurocognitive domains and appetite-regulating circuits in female patients with AN.
The investigators aim at assessing peripheral concentrations of neuroendocrinological components of the Hypothalamus-Pituitary-Gonadal (HPG) and Hypothalamus-Pituitary-Adrenal (HPA) axis, as well as appetite-regulating hormones in AN and to examine associations with AN-associated psychopathology and neurocognitive performances before (baseline), during and after inpatient psychotherapy of female patients receiving concomitant treatment with estrogens (vs. placebo).
Detailed Description
While there is broad knowledge on the disruption of appetite regulation, neurocognitive deficits in AN patients, the impact of cortisol on neurocognitive performances in patients with AN and the effects of estrogen on neurocognitive features in healthy subjects, up to now, no study has implemented estrogen replacement in AN patients, in order to examine ist effects upon AN-associated psychopathology, neurocognition and peptides regulating appetite. Thus, this is the first study of its kind.
Primary target: Assessment of the impact of sexual hormone replacement using an estrogen-progestin-combination as add-on to psychotherapy upon neurocognitive performance in patients suffering from anorexia nervosa by means of a neuropsychological test battery consisting of a test of verbal intelligence, the Trail making test A and B, a Go/No-go paradigm and the Wisconsin Card Sorting Test.
Secondary targets:
Examination of safety and tolerability of sexual hormone replacement using an estrogen-progestin-combination in patients with anorexia nervosa.
Assessment of the impact of the sexual hormone replacement upon psychopathology in patients with anorexia nervosa by means of the Eating Disorder Examination Questionnaire (EDE-Q) and the Eating Disorder Inventory-2 (EDI-2).
Assessment of the impact of substitution upon anxiety (STAI)
Assessment of the impact on cortisol levels
Assessment of the impact on appetite-regulating plasma peptides
Assessment of the impact on the prescription of antidepressants
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Anorexia Nervosa
Keywords
anorexia nervosa, estrogen, psychotherapy, cortisol, appetite regulation, neurocognitive performance, eating disorder, sexual hormone
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
randomized, placebo-controlled Phase IIa clinical trial in patients with anorexia nervosa
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
double-blinded study
Allocation
Randomized
Enrollment
11 (Actual)
8. Arms, Groups, and Interventions
Arm Title
verum group
Arm Type
Active Comparator
Arm Description
approved oral contraceptive: ethinyl estradiol 0.03mg and dienogest 2mg (combination drug) daily intake over 10 weeks
Arm Title
placebo group
Arm Type
Placebo Comparator
Arm Description
placebo
Intervention Type
Drug
Intervention Name(s)
ethinyl estradiol 0.03mg and dienogest 2 mg (combination)
Intervention Description
approved oral contraceptive (Germany): Maxim
Intervention Type
Drug
Intervention Name(s)
Placebo oral capsule
Intervention Description
placebo
Primary Outcome Measure Information:
Title
Changes in neurocognitive performance
Description
Performance based on a neurocognitive test battery
Time Frame
10 weeks of hormonal substitution with an estrogen-progestin-combination
Secondary Outcome Measure Information:
Title
Incidence of treatment-emergent adverse Events (AE) (safety/tolerability)
Description
Number of adverse events (including AE, AR, severe AE, SAR and SUSAR)
Time Frame
10 weeks of hormonal substitution with an estrogen-progestin-combination
Title
Changes in psychopathology (EDE-Q)
Description
Changes in sum scores in the EDE-Q
Time Frame
10 weeks of hormonal substitution with an estrogen-progestin-combination
Title
Changes in psychopathology (EDI-2)
Description
Changes in sum scores in the EDI-2
Time Frame
10 weeks of hormonal substitution with an estrogen-progestin-combination
Title
Changes in psychopathology (STAI)
Description
Changes in sum scores in the STAI
Time Frame
10 weeks of hormonal substitution with an estrogen-progestin-combination
Title
Changes in psychopathology (Patient Health Questionnaire-9, PHQ-9)
Description
Changes in sum scores in the PHQ-9
Time Frame
10 weeks of hormonal substitution with an estrogen-progestin-combination
Title
Changes in psychopathology (Eating Disorder Quality of Life, EDQoL)
Description
Changes in sum scores in the EDQoL
Time Frame
10 weeks of hormonal substitution with an estrogen-progestin-combination
Title
Neuroendocrinological changes (cortisol)
Description
Changes in plasma cortisol levels during a dexamethasone suppression test
Time Frame
10 weeks of hormonal substitution with an estrogen-progestin-combination
Title
Neuroendocrinological changes (glucose)
Description
Changes in plasma concentrations of glucose
Time Frame
10 weeks of hormonal substitution with an estrogen-progestin-combination
Title
Neuroendocrinological changes (insulin)
Description
Changes in plasma concentrations of insulin
Time Frame
10 weeks of hormonal substitution with an estrogen-progestin-combination
Title
Neuroendocrinological changes (ghrelin)
Description
Changes in plasma concentrations of the appetite-regulating peptide ghrelin
Time Frame
10 weeks of hormonal substitution with an estrogen-progestin-combination
Title
Neuroendocrinological changes (leptin)
Description
Changes in plasma concentrations of the appetite-regulating peptide leptin
Time Frame
10 weeks of hormonal substitution with an estrogen-progestin-combination
Title
Changes in antidepressant medication
Description
Changes in antidepressants´ use
Time Frame
10 weeks of hormonal substitution with an estrogen-progestin-combination
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
anorexia nervosa according to the Diagnostic and Statistical Manual of Mental Disorders (DSM V) or subsyndromal anorexia nervosa (lack of a diagnostic symptom according to DSM V)
BMI ≥ 13 kg/m2 and ≤ 18.5 kg/m2
able to provide written informed consent
Exclusion Criteria:
a known hypersensitivity to the active compound or to other components of the study drug
one or more contraindications for the use of hormonal contraception: Smoking over 20 cigarettes/day; Acute venous thromboembolic disease or increased risk; Known hereditary or acquired predisposition for venous thrombosis, e.g. activated protein C (APC)-resistance (including factor V Leiden Mutation), antithrombin III deficiency, protein C deficiency, protein S deficiency; Risk for arterial thromboembolism (diabetes mellitus with vascular sequelae, severe hypertonus, severe dyslipoproteinemia); Known hereditary or acquired predisposition for arterial thrombosis, e.g. hyperhomocysteinemia and anti-phospholipid antibodies (anticardiolipin antibodies, Lupus anticoagulants); Cerebrovascular disease (past cerebral infarction or prodromal states such as transitory ischemia attacks); Past migraine with focal neurological symptoms; Liver disease or pancreatitis; Dubin-Johnson syndrome and Rotor syndrome; Known porphyria; Known or suspected sexual hormone sensitive tumors; Unresolved vaginal bleeding
a present severe depressive episode (major depression) according to the DSM V
past or present alcohol or drug abuse
severe psychiatric disorders (axis I) according to the DSM V (such as bipolar affective disorder or schizophrenia) in addition to anorexia nervosa
suicidality
known diabetes mellitus
severe somatic comorbidity or organ dysfunction that is not compatible with intake of the study drug
use of hormonal depot compounds (injectable drugs, implants), or hormonal intrauterine pessaries during the last four weeks before the screening visit (V1)
pregnancy
breastfeeding during the last 6 months before V1
Facility Information:
Facility Name
Department of Psychosomatic Medicine and Psychotherapy, University Hospital Erlangen
City
Erlangen
State/Province
Bavaria
ZIP/Postal Code
91054
Country
Germany
12. IPD Sharing Statement
Citations:
PubMed Identifier
29631553
Citation
Paslakis G, Maas S, Gebhardt B, Mayr A, Rauh M, Erim Y. Prospective, randomized, double-blind, placebo-controlled phase IIa clinical trial on the effects of an estrogen-progestin combination as add-on to inpatient psychotherapy in adult female patients suffering from anorexia nervosa. BMC Psychiatry. 2018 Apr 10;18(1):93. doi: 10.1186/s12888-018-1683-1.
Results Reference
derived
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Estrogen Replacement in Anorexia Nervosa
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