Clinical trial NCT03172533: Estrogen Replacement in Anorexia Nervosa
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
Overall status: TERMINATED
Phase: PHASE2
Conditions: Anorexia Nervosa
Keywords: anorexia nervosa
estrogen
psychotherapy
cortisol
appetite regulation
neurocognitive performance
eating disorder
sexual hormone
Lead sponsor: University of Erlangen-Nürnberg Medical School
Sponsor class: OTHER
First posted: 2017-06-01
Enrollment: 11
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: randomized, placebo-controlled Phase IIa clinical trial in patients with anorexia nervosa
Primary purpose: TREATMENT

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

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

Primary outcomes:
measure: Changes in neurocognitive performance
timeFrame: 10 weeks of hormonal substitution with an estrogen-progestin-combination
Secondary outcomes:
measure: Incidence of treatment-emergent adverse Events (AE) (safety/tolerability)
timeFrame: 10 weeks of hormonal substitution with an estrogen-progestin-combination
measure: Changes in psychopathology (EDE-Q)
timeFrame: 10 weeks of hormonal substitution with an estrogen-progestin-combination
measure: Changes in psychopathology (EDI-2)
timeFrame: 10 weeks of hormonal substitution with an estrogen-progestin-combination
measure: Changes in psychopathology (STAI)
timeFrame: 10 weeks of hormonal substitution with an estrogen-progestin-combination
measure: Changes in psychopathology (Patient Health Questionnaire-9, PHQ-9)
timeFrame: 10 weeks of hormonal substitution with an estrogen-progestin-combination
measure: Changes in psychopathology (Eating Disorder Quality of Life, EDQoL)
timeFrame: 10 weeks of hormonal substitution with an estrogen-progestin-combination
measure: Neuroendocrinological changes (cortisol)
timeFrame: 10 weeks of hormonal substitution with an estrogen-progestin-combination
measure: Neuroendocrinological changes (glucose)
timeFrame: 10 weeks of hormonal substitution with an estrogen-progestin-combination
measure: Neuroendocrinological changes (insulin)
timeFrame: 10 weeks of hormonal substitution with an estrogen-progestin-combination
measure: Neuroendocrinological changes (ghrelin)
timeFrame: 10 weeks of hormonal substitution with an estrogen-progestin-combination
measure: Neuroendocrinological changes (leptin)
timeFrame: 10 weeks of hormonal substitution with an estrogen-progestin-combination
measure: Changes in antidepressant medication
timeFrame: 10 weeks of hormonal substitution with an estrogen-progestin-combination
Other outcomes:
Locations:
city: Erlangen
country: Germany
facility: Department of Psychosomatic Medicine and Psychotherapy, University Hospital Erlangen
state: Bavaria
Study officials:
References:
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.