Clinical trial NCT06027567: The Effect of an Anti-obesity Drug, Semaglutide, As Treatment in New-onset Idiopathic Intracranial Hypertension (IIH) Compared to Standard Weight Management (dietician) with Regards to Change in Weight and Intracranial Pressure
Official title: Glucagon-like Peptide-1 Receptor (GLP-1R) Analogue Assisted Rapid Weight Loss Program As Treatment of Idiopathic Intracranial Hypertension
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Idiopathic Intracranial Hypertension
Intracranial Pressure
Obesity
Pseudotumor Cerebri Syndrome
Papilledema
Weight Loss
Keywords: Idiopathic Intracranial Hypertension
Papilledema
Weight loss
Obesity
Pseudotumor Cerebri Syndrome
Intracranial Pressure
Lead sponsor: Danish Headache Center
Sponsor class: OTHER
Collaborators: name: Rigshospitalet, Denmark
name: Odense University Hospital
name: University of Copenhagen
First posted: 2023-09-07
Enrollment: 50
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Open label randomized controlled clinical treatment trial Patients are randomly assigned 1:1 to standard-of-care or intervention
Primary purpose: TREATMENT

Brief summary: 50 patients with verified new-onset Idiopathic Intracranial Hypertension are randomly allocated to standard weight management (dietician counselling) or trial intervention consisting of subcutaneous injections with Semaglutide for 10 months combined, in the initial 8 weeks following diagnosis, with a Very Low Calorie-Diet (max 800 kcal/day)

Detailed description: Idiopathic Intracranial Hypertension is primarily observed in obese female and weight management promotes disease control by yet unsettled mechanisms. Effective, fast and lasting weight loss is crucial, however, hard to achieve. Current weight management strategy in IIH in Denmark is counselling by a dietician. This study investigates whether an initial Very Low Calorie Diet (max 800 kcal/day) for 8 weeks following the diagnosis combined with GLP1-RA treatment throughout 10 months is tolerated and more efficient in achieving substantial weight loss and reduction of intracranial pressure. Furthermore, a number of secondary outcomes are measured including headache burden, quality of life, structure and function of the optic nerve, non-invasive surrogate markers of intracranial pressure, body fat mass, bone health, fatty liver disease and a range of cerebrospinal-, blood- and urine markers of i.a. the hormonal, inflammatory, metabolic, and headache biomarker profile.

The intervention may candidate as a future first-line treatment regime.

Eligibility criteria: Inclusion Criteria:

* Confirmed new onset definite IIH with papilledema and lumbar opening pressure ≥25 cm cerebrospinal fluid according to Friedmann diagnostic criteria
* BMI ≥ 27
* Use of contraceptive methods with failure rates of less than 1 % throughout the study period for group A and for at least an additional 2 months after cessation of Semaglutide
* Written, informed consent

Exclusion Criteria:

* Unable to provide written informed consent or participate
* Malignant IIH with visual threat that requires surgical intervention, i.e., cerebrospinal fluid diversion (shunting), optic nerve sheet fenestration or cerebral venous sinus stenting
* Pregnancy or breastfeeding
* Treatment with antidiabetics, blood-thinners or medication that may increase the risk of adverse events
* Diabetes, congestive heart failure, severe vascular disease, pancreatitis, severe ophthalmological disorders other than IIH (e.g. retinopathy)
* History or family history of thyroid carcinomas or Multiple Endocrine Neoplasias (MEN1/MEN2)
* History of bariatric surgery
* Known hypersensitivity to any contents of Semaglutide®
* Other severe/uncontrolled mental or physical disease

Primary outcomes:
measure: Weight
timeFrame: 8 weeks
measure: Intracranial pressure
timeFrame: 8 weeks
measure: Intracranial pressure
timeFrame: 8 weeks
Secondary outcomes:
measure: Weight
timeFrame: 10 months
measure: Intracranial Pressure
timeFrame: 10 months
measure: Intracranial Pressure
timeFrame: 10 months
measure: Quality of Life
timeFrame: 8 weeks + 10 months
measure: Headache burden measured by HURT questionnaire
timeFrame: 8 weeks + 10 months
measure: Change in Papilledema
timeFrame: 8 weeks + 10 months
measure: Visual fields
timeFrame: 8 weeks + 10 months
measure: EDI-OCT
timeFrame: 8 weeks + 10 months
measure: Optic disc elevation
timeFrame: Baseline + 8 weeks + 10 months
measure: Remission
timeFrame: 8 weeks + 10 months
measure: Change in fat mass
timeFrame: 8 weeks + 10 months
measure: Total fat mass
timeFrame: Baseline + 8 weeks + 10 months
measure: Feasibility
timeFrame: 8 weeks + 10 months
measure: Need of intracranial pressure-lowering medication_1
timeFrame: 8 weeks + 10 months
measure: Fatty liver prevalence
timeFrame: Baseline + 8 weeks + 10 months
measure: Monthly headache days
timeFrame: Baseline + 8 weeks + 10 months
measure: Headche severity
timeFrame: Baseline + 8 weeks + 10 months
measure: Headache medication - Acute analgesic use
timeFrame: Baseline + 8 weeks + 10 months
measure: Headache medication - preventive medication
timeFrame: Baseline + 8 weeks + 10 months
measure: Optic nerve sheath diameter
timeFrame: Baseline + 8 weeks + 10 months
measure: Peripapillary capillary density
timeFrame: Baseline + 8 weeks + 10 months
measure: Peripapillary artery-to-venule ratio
timeFrame: Baseline + 8 weeks + 10 months
measure: Truncal fat
timeFrame: Baseline + 8 weeks + 10 months
measure: Android-gynoid-ratio
timeFrame: Baseline + 8 weeks and 10 months
measure: Adverse events
timeFrame: 8 weeks + 10 months
measure: Need of intracranial pressure-lowering medication_2
timeFrame: Baseline + 8 weeks + 10 months
measure: Insulin like-Growth-Factor-1
timeFrame: Baseline
measure: Insulinlike Growth Factor Binding Protein-3
timeFrame: Baseline
measure: Growth hormone
timeFrame: Baseline
measure: Lutropin
timeFrame: Baseline
measure: Follitropin
timeFrame: Baseline
measure: Testosteron
timeFrame: Baseline
measure: Estradiol
timeFrame: Baseline
measure: Sex-Hormone Binding Globulin
timeFrame: Baseline
measure: Anti-Müllerian Hormone
timeFrame: Baseline
measure: Dehydroepiandrosterone
timeFrame: Baseline
measure: Androstenedion
timeFrame: Baseline
measure: 17-hydroxyprogesterone (mg/d)
timeFrame: Baseline
measure: Cortisol 0 min
timeFrame: Baseline
measure: Cortisol 30 min
timeFrame: Baseline
measure: Pituitary adenylate cyclase-activating peptide (PACAP) Pituitary adenylate cyclase-activating peptide Pituitary adenylate cyclase-activating peptide
timeFrame: Baseline + 8 weeks + 10 months
measure: Calcitonin Gene Related Peptide
timeFrame: Baseline + 8 weeks + 10 months
measure: Change in bone marker (CTX)
timeFrame: Baseline + 8 weeks + 10 months
measure: Change in bone marker (PiNP)
timeFrame: baseline + 8 weeks + 10 months
measure: Regional bone density
timeFrame: Baseline + 8 weeks + 10 months
measure: Androgen metabolism_1
timeFrame: Baseline + 8 weeks + 10 months
measure: Androgen metabolism_2
timeFrame: Baseline + 8 weeks + 10 months
measure: Androgen metabolism_3
timeFrame: Baseline + 8 weeks + 10 months
measure: Androgen metabolism_4
timeFrame: Baseline + 8 weeks + 10 months
measure: Androgen metabolism_5
timeFrame: Baseline + 8 weeks + 10 months
measure: Intrathecal Semaglutide
timeFrame: 10 months
measure: Ammoniaemia_1
timeFrame: Baseline + 8 weeks + 10 months
measure: Ammoniaemia_2
timeFrame: Baseline + 8 weeks + 10 months
measure: Ketosis
timeFrame: 8 weeks + 10 months
measure: Change in metabolic parameters
timeFrame: 8 weeks + 10 months
measure: Change in metabolic parameters
timeFrame: 8 weeks + 10 months
Other outcomes:
measure: Omics
timeFrame: Baseline + 8 weeks + 10 months
Locations:
city: Glostrup
country: Denmark
facility: Danish Headache Center, Department of Neurology, Rigshospitalet
city: Odense
country: Denmark
facility: Headache clinic, Department of Neurology, Odense University Hospital
Study officials:
affiliation: Danish Headache Center
name: Rigmor H Jensen, Professor
role: STUDY_DIRECTOR
References: