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)
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
38
Subcutaneous once-weekly injections of Semaglutide uptitrating to a maximum of 2.4 mg
Very Low Calorie Diet (max 800 kcal/day) using Nupo Diet meal replacement products
Counselling by a dietician on weight loss through behavioural changes and life style intervention
Headache clinic, Department of Neurology, Odense University Hospital
Odense, Odense, Denmark
Danish Headache Center, Department of Neurology, Rigshospitalet
Glostrup Municipality, Denmark
Weight
Weight change (%)
Time frame: 8 weeks
Intracranial pressure
Change in lumbar opening pressure in cm cerebrospinal fluid measured by manometry
Time frame: 8 weeks
Intracranial pressure
Change in lumbar opening pressure (%)
Time frame: 8 weeks
Weight
Weight change (%)
Time frame: 10 months
Intracranial Pressure
Change in lumbar opening pressure in cm cerebrospinal fluid measured by manometry
Time frame: 10 months
Intracranial Pressure
Change in lumbar opening pressure (%)
Time frame: 10 months
Quality of Life
Change in total score of Quality of Life (psychological, social, physical, environmental) assessed by the World Health Organization Quality of Life Brief Version Questionnaire (0-100; 0 worst, 100 best)
Time frame: 8 weeks + 10 months
Headache burden measured by HURT questionnaire
Change in summation of scores in the questionnaire "Headache Under Response to Treatment Questionnaire" (HURT); 0-24 points were higher numbers are worse outcome
Time frame: 8 weeks + 10 months
Change in Papilledema
Change in Frisén Grade (0-5, 0 minimal, 5 worst)
Time frame: 8 weeks + 10 months
Visual fields
Perimetric mean deviation (decibel) by Humphrey automated perimetry
Time frame: 8 weeks + 10 months
EDI-OCT
Change in Papillary thickness (um) measured by Enhanced Depth Imaging Optical Coherence Tomography (EDI-OCT)
Time frame: 8 weeks + 10 months
Optic disc elevation
Optic disc elevation (mm) measured by transorbital ultrasonography, (average of 3 scans of each eye with papilledema)
Time frame: Baseline + 8 weeks + 10 months
Remission
Proportion of patients with abscence of papilledema with or without intracranial pressure \<25 cm cerebrospinal fluid
Time frame: 8 weeks + 10 months
Change in fat mass
Change in body fat percentage measured by Dual Energy X-ray Absorptiometry compared to baseline
Time frame: 8 weeks + 10 months
Total fat mass
Body fat percentage measured by Dual Energy X-ray Absorptiometry
Time frame: Baseline + 8 weeks + 10 months
Feasibility
Drop-out rate (proportion of patients withdrawing from participation)
Time frame: 8 weeks + 10 months
Need of intracranial pressure-lowering medication_1
Dose (mg) of intracranial pressure-lowering medication needed (Acetazolamide, Topiramate, diuretics)
Time frame: 8 weeks + 10 months
Fatty liver prevalence
Prevalence of non-alcoholic fatty liver disease evaluated by ultrasonography (subjectively assessed density of liver parenchyma compared to hepatic perivascular density and renal density), assessed by an experienced radiologist with specialization in ultrasonography
Time frame: Baseline + 8 weeks + 10 months
Monthly headache days
Number of days with headache for the past 30 days preceding visit
Time frame: Baseline + 8 weeks + 10 months
Headche severity
Number of days with mild, moderate, and severy headache, respectively, in the past 30 days preceding visit
Time frame: Baseline + 8 weeks + 10 months
Headache medication - Acute analgesic use
Number of days with need of acute analgesic treatment for headache
Time frame: Baseline + 8 weeks + 10 months
Headache medication - preventive medication
Need of preventive medical treatment for headache
Time frame: Baseline + 8 weeks + 10 months
Optic nerve sheath diameter
Optic nerve sheath diameter (mm) measured by transorbital ultrasonography (average of 3 scans of each eye with papilledema)
Time frame: Baseline + 8 weeks + 10 months
Peripapillary capillary density
Change in peripapillary capillary density (ratio of pixels of perpapillary vessels and pixels in the foveal area evaluated by Optic Coherence Tomography Angiography
Time frame: Baseline + 8 weeks + 10 months
Peripapillary artery-to-venule ratio
Change in peripapillary artery-to-venule diameter ratio measured by confocal Scanning Laser Ophtalmoscopy
Time frame: Baseline + 8 weeks + 10 months
Truncal fat
Change in percentage of truncal adiposity measured by Dual Energy X-ray Absorptiometry
Time frame: Baseline + 8 weeks + 10 months
Android-gynoid-ratio
Change in ratio of Android versus gynoid fat percentage using Dual Energy X-ray Absorptiometry
Time frame: Baseline + 8 weeks and 10 months
Adverse events
Number of adverse events overall, and sub-categorized into adverse events (AE) (any event happening during attachment to the project) and severe adverse events (SAE) in case of the following conditions: Hospitalization or prolongation of hospitalization, death, life-threatening or significant disability/incapacity
Time frame: 8 weeks + 10 months
Need of intracranial pressure-lowering medication_2
Number of patients in need of any intracranial pressure-lowering drug (Acetazolamide, Topiramate, diuretics)
Time frame: Baseline + 8 weeks + 10 months
Insulin like-Growth-Factor-1
Level of Insulin like-Growth-Factor-1 in serum (ug/L) in women not taking estrogen-containing contraceptives.
Time frame: Baseline
Insulinlike Growth Factor Binding Protein-3
Level of Insulinlike Growth Factor Binding Protein-3 in serum (ug/L) in women not taking estrogen-containing contraceptives.
Time frame: Baseline
Growth hormone
Level of growth hormone in serum ug(L) in women not taking estrogen-containing contraceptives.
Time frame: Baseline
Lutropin
Level of Lutropin in serum (IU/L) in women not taking estrogen-containing contraceptives.
Time frame: Baseline
Follitropin
Level of Follitropin in serum (IU/L) in women not taking estrogen-containing contraceptives.
Time frame: Baseline
Testosteron
Level of testosteron in serum (nmol/L) in women not taking estrogen-containing contraceptives.
Time frame: Baseline
Estradiol
Level of estradiol in serum (nmol/L) in women not taking estrogen-containing contraceptives.
Time frame: Baseline
Sex-Hormone Binding Globulin
Level of Sex-Hormone Binding Globulin in serum (nmol/L) in women not taking estrogen-containing contraceptives.
Time frame: Baseline
Anti-Müllerian Hormone
Level of Anti-Müllerian Hormone (pmol/L) in serum in women not taking estrogen-containing contraceptives.
Time frame: Baseline
Dehydroepiandrosterone
Level of Dehydroepiandrosterone (DHEAS) in serum (umol/L) in women not taking estrogen-containing contraceptives.
Time frame: Baseline
Androstenedion
Level of androstenedion (nmol/L) in serum in women not taking estrogen-containing contraceptives.
Time frame: Baseline
17-hydroxyprogesterone (mg/d)
Level of 17-hydroxyprogesterone (mg/d) in serum in women not taking estrogen-containing contraceptives.
Time frame: Baseline
Cortisol 0 min
Level of cortisol (nmol/L) in serum in women not taking estrogen-containing contraceptives.
Time frame: Baseline
Cortisol 30 min
Level of cortisol (nmol/L) in serum 30 minutes after stimulation with 0,25 mg SynACHTen in women not taking estrogen-containing contraceptives.
Time frame: Baseline
Pituitary adenylate cyclase-activating peptide (PACAP) Pituitary adenylate cyclase-activating peptide Pituitary adenylate cyclase-activating peptide
Level (picograms per milliliter in plasma and cerebrospinal fluid) of Pituitary adenylate cyclase-activating peptide (PACAP)
Time frame: Baseline + 8 weeks + 10 months
Calcitonin Gene Related Peptide
Calcitonin Gene Related Peptide (CGRP) level pg/mL (picograms per milliliter in plasma and cerebrospinal fluid)
Time frame: Baseline + 8 weeks + 10 months
Change in bone marker (CTX)
Change in carboxy-terminal collagen crosslinks (CTX) level (nanograms per liter)
Time frame: Baseline + 8 weeks + 10 months
Change in bone marker (PiNP)
Change in procollagen type I N-propeptide (PiNP) level (micrograms per liter) compared to baseline
Time frame: baseline + 8 weeks + 10 months
Regional bone density
Change in regional bone density in grams/square cm (g/cm2) and T- and Z-scores of hip and spine measured by Dual Energy X-ray Absorptiometry compared to baseline
Time frame: Baseline + 8 weeks + 10 months
Androgen metabolism_1
Ratio between Etiocholanolone and Androsterone (ng/mg) in 24-hour urine
Time frame: Baseline + 8 weeks + 10 months
Androgen metabolism_2
Ratio between 5-alpha-tetrahydrocortisol (5a-THF) and tetrahydrocortisol (THF) in 24-hour urine
Time frame: Baseline + 8 weeks + 10 months
Androgen metabolism_3
Level of testosterone in 24-hour urine (ng/L)
Time frame: Baseline + 8 weeks + 10 months
Androgen metabolism_4
Level of 3-alpha-androstanediol in 24-hour urine (nmol/L)
Time frame: Baseline + 8 weeks + 10 months
Androgen metabolism_5
Level of 11-oxygenated androgens (11-OHA4) (pg/L) in 24-hour urine
Time frame: Baseline + 8 weeks + 10 months
Intrathecal Semaglutide
Level of semaglutide in cerebrospinal fluid (picomol/L)
Time frame: 10 months
Ammoniaemia_1
Levels of plasma ammonium (umol/L)
Time frame: Baseline + 8 weeks + 10 months
Ammoniaemia_2
Correlation between plasma ammonium (umol/L) and presence of fatty liver disease as indicated by liver ultrasonography
Time frame: Baseline + 8 weeks + 10 months
Ketosis
Proportion of patients in ketosis measured by urine stix
Time frame: 8 weeks + 10 months
Change in metabolic parameters
Change in Homeostatic Model for Insulin Resistance (HOMA2IR) compared to baseline
Time frame: 8 weeks + 10 months
Change in metabolic parameters
Change in glycated hemoglobin (mmol/mol) compared to baseline
Time frame: 8 weeks + 10 months
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