HOSAN: Estrogen Replacement in Anorexia Nervosa

Sponsor

University of Erlangen-Nürnberg Medical School (Other)

Overall Status

Terminated

CT.gov ID

NCT03172533

Collaborator

(none)

Enrollment

Location

Arms

Actual Duration (Months)

0.3

Patients Per Site Per Month

Study Details

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).

Condition or Disease	Intervention/Treatment	Phase
Anorexia Nervosa	Drug: ethinyl estradiol 0.03mg and dienogest 2 mg (combination) Drug: Placebo oral capsule	Phase 2

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

Study Design

Study Type:

Interventional

Actual Enrollment :

11 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

randomized, placebo-controlled Phase IIa clinical trial in patients with anorexia nervosarandomized, placebo-controlled Phase IIa clinical trial in patients with anorexia nervosa

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

double-blinded study

Primary Purpose:

Treatment

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

Actual Study Start Date :

Mar 15, 2016

Actual Primary Completion Date :

Jan 15, 2019

Actual Study Completion Date :

Jan 15, 2019

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: verum group approved oral contraceptive: ethinyl estradiol 0.03mg and dienogest 2mg (combination drug) daily intake over 10 weeks	Drug: ethinyl estradiol 0.03mg and dienogest 2 mg (combination) approved oral contraceptive (Germany): Maxim
Placebo Comparator: placebo group placebo	Drug: Placebo oral capsule placebo

Arm

Intervention/Treatment

Active Comparator: verum group

approved oral contraceptive: ethinyl estradiol 0.03mg and dienogest 2mg (combination drug) daily intake over 10 weeks

Drug: ethinyl estradiol 0.03mg and dienogest 2 mg (combination)

approved oral contraceptive (Germany): Maxim

Placebo Comparator: placebo group

placebo

Drug: Placebo oral capsule

placebo

Outcome Measures

Primary Outcome Measures

Changes in neurocognitive performance [10 weeks of hormonal substitution with an estrogen-progestin-combination]
Performance based on a neurocognitive test battery

Secondary Outcome Measures

Incidence of treatment-emergent adverse Events (AE) (safety/tolerability) [10 weeks of hormonal substitution with an estrogen-progestin-combination]
Number of adverse events (including AE, AR, severe AE, SAR and SUSAR)
Changes in psychopathology (EDE-Q) [10 weeks of hormonal substitution with an estrogen-progestin-combination]
Changes in sum scores in the EDE-Q
Changes in psychopathology (EDI-2) [10 weeks of hormonal substitution with an estrogen-progestin-combination]
Changes in sum scores in the EDI-2
Changes in psychopathology (STAI) [10 weeks of hormonal substitution with an estrogen-progestin-combination]
Changes in sum scores in the STAI
Changes in psychopathology (Patient Health Questionnaire-9, PHQ-9) [10 weeks of hormonal substitution with an estrogen-progestin-combination]
Changes in sum scores in the PHQ-9
Changes in psychopathology (Eating Disorder Quality of Life, EDQoL) [10 weeks of hormonal substitution with an estrogen-progestin-combination]
Changes in sum scores in the EDQoL
Neuroendocrinological changes (cortisol) [10 weeks of hormonal substitution with an estrogen-progestin-combination]
Changes in plasma cortisol levels during a dexamethasone suppression test
Neuroendocrinological changes (glucose) [10 weeks of hormonal substitution with an estrogen-progestin-combination]
Changes in plasma concentrations of glucose
Neuroendocrinological changes (insulin) [10 weeks of hormonal substitution with an estrogen-progestin-combination]
Changes in plasma concentrations of insulin
Neuroendocrinological changes (ghrelin) [10 weeks of hormonal substitution with an estrogen-progestin-combination]
Changes in plasma concentrations of the appetite-regulating peptide ghrelin
Neuroendocrinological changes (leptin) [10 weeks of hormonal substitution with an estrogen-progestin-combination]
Changes in plasma concentrations of the appetite-regulating peptide leptin
Changes in antidepressant medication [10 weeks of hormonal substitution with an estrogen-progestin-combination]
Changes in antidepressants´ use

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 45 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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