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
- Conditions
- Idiopathic Intracranial HypertensionIntracranial PressureObesityPseudotumor Cerebri SyndromePapilledemaWeight Loss
- Interventions
- Registration Number
- NCT06027567
- Lead Sponsor
- Rigmor Højland Jensen
- 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- Female
- Target Recruitment
- 50
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Semaglutide Very Low Calorie Diet Semaglutide up-titration to 2.4 mg for 10 months initially combined with a Very Low Calorie Diet (800 kcal/day) for 8 weeks. Counselling by dietician Standard medical treatment of intracranial hypertension Semaglutide Dietician counselling Semaglutide up-titration to 2.4 mg for 10 months initially combined with a Very Low Calorie Diet (800 kcal/day) for 8 weeks. Counselling by dietician Standard medical treatment of intracranial hypertension Standard care (dietician) Dietician counselling Standard weight loss intervention Counselling by dietician Standard medical treatment of intracranial hypertension Semaglutide Semaglutide Semaglutide up-titration to 2.4 mg for 10 months initially combined with a Very Low Calorie Diet (800 kcal/day) for 8 weeks. Counselling by dietician Standard medical treatment of intracranial hypertension
- Primary Outcome Measures
Name Time Method Weight 8 weeks Weight change (%)
Intracranial pressure 8 weeks Change in lumbar opening pressure (%)
- Secondary Outcome Measures
Name Time Method Weight 10 months Weight change (%)
Remission 8 weeks + 10 months Proportion of patients with abscence of papilledema with or without intracranial pressure \<25 cm cerebrospinal fluid
Change in fat mass 8 weeks + 10 months Change in body fat percentage measured by Dual Energy X-ray Absorptiometry compared to baseline
Change in Papilledema 8 weeks + 10 months Change in Frisén Grade (0-5, 0 minimal, 5 worst)
Total fat mass Baseline + 8 weeks + 10 months Body fat percentage measured by Dual Energy X-ray Absorptiometry
Feasibility 8 weeks + 10 months Drop-out rate (proportion of patients withdrawing from participation)
Need of intracranial pressure-lowering medication_1 8 weeks + 10 months Dose (mg) of intracranial pressure-lowering medication needed (Acetazolamide, Topiramate, diuretics)
Fatty liver prevalence Baseline + 8 weeks + 10 months 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
Monthly headache days Baseline + 8 weeks + 10 months Number of days with headache for the past 30 days preceding visit
Headche severity Baseline + 8 weeks + 10 months Number of days with mild, moderate, and severy headache, respectively, in the past 30 days preceding visit
Intracranial Pressure 10 months Change in lumbar opening pressure (%)
Quality of Life 8 weeks + 10 months 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)
Peripapillary capillary density Baseline + 8 weeks + 10 months Change in peripapillary capillary density (ratio of pixels of perpapillary vessels and pixels in the foveal area evaluated by Optic Coherence Tomography Angiography
Peripapillary artery-to-venule ratio Baseline + 8 weeks + 10 months Change in peripapillary artery-to-venule diameter ratio measured by confocal Scanning Laser Ophtalmoscopy
Truncal fat Baseline + 8 weeks + 10 months Change in percentage of truncal adiposity measured by Dual Energy X-ray Absorptiometry
Headache burden measured by HURT questionnaire 8 weeks + 10 months Change in summation of scores in the questionnaire "Headache Under Response to Treatment Questionnaire" (HURT); 0-24 points were higher numbers are worse outcome
Visual fields 8 weeks + 10 months Perimetric mean deviation (decibel) by Humphrey automated perimetry
EDI-OCT 8 weeks + 10 months Change in Papillary thickness (um) measured by Enhanced Depth Imaging Optical Coherence Tomography (EDI-OCT)
Optic disc elevation Baseline + 8 weeks + 10 months Optic disc elevation (mm) measured by transorbital ultrasonography, (average of 3 scans of each eye with papilledema)
Headache medication - Acute analgesic use Baseline + 8 weeks + 10 months Number of days with need of acute analgesic treatment for headache
Headache medication - preventive medication Baseline + 8 weeks + 10 months Need of preventive medical treatment for headache
Optic nerve sheath diameter Baseline + 8 weeks + 10 months Optic nerve sheath diameter (mm) measured by transorbital ultrasonography (average of 3 scans of each eye with papilledema)
Android-gynoid-ratio Baseline + 8 weeks and 10 months Change in ratio of Android versus gynoid fat percentage using Dual Energy X-ray Absorptiometry
Adverse events 8 weeks + 10 months 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
Need of intracranial pressure-lowering medication_2 Baseline + 8 weeks + 10 months Number of patients in need of any intracranial pressure-lowering drug (Acetazolamide, Topiramate, diuretics)
Insulin like-Growth-Factor-1 Baseline Level of Insulin like-Growth-Factor-1 in serum (ug/L) in women not taking estrogen-containing contraceptives.
Insulinlike Growth Factor Binding Protein-3 Baseline Level of Insulinlike Growth Factor Binding Protein-3 in serum (ug/L) in women not taking estrogen-containing contraceptives.
Growth hormone Baseline Level of growth hormone in serum ug(L) in women not taking estrogen-containing contraceptives.
Lutropin Baseline Level of Lutropin in serum (IU/L) in women not taking estrogen-containing contraceptives.
Follitropin Baseline Level of Follitropin in serum (IU/L) in women not taking estrogen-containing contraceptives.
Testosteron Baseline Level of testosteron in serum (nmol/L) in women not taking estrogen-containing contraceptives.
Estradiol Baseline Level of estradiol in serum (nmol/L) in women not taking estrogen-containing contraceptives.
Sex-Hormone Binding Globulin Baseline Level of Sex-Hormone Binding Globulin in serum (nmol/L) in women not taking estrogen-containing contraceptives.
Dehydroepiandrosterone Baseline Level of Dehydroepiandrosterone (DHEAS) in serum (umol/L) in women not taking estrogen-containing contraceptives.
Anti-Müllerian Hormone Baseline Level of Anti-Müllerian Hormone (pmol/L) in serum in women not taking estrogen-containing contraceptives.
Androstenedion Baseline Level of androstenedion (nmol/L) in serum in women not taking estrogen-containing contraceptives.
17-hydroxyprogesterone (mg/d) Baseline Level of 17-hydroxyprogesterone (mg/d) in serum in women not taking estrogen-containing contraceptives.
Cortisol 0 min Baseline Level of cortisol (nmol/L) in serum in women not taking estrogen-containing contraceptives.
Cortisol 30 min Baseline Level of cortisol (nmol/L) in serum 30 minutes after stimulation with 0,25 mg SynACHTen in women not taking estrogen-containing contraceptives.
Pituitary adenylate cyclase-activating peptide (PACAP) Pituitary adenylate cyclase-activating peptide Pituitary adenylate cyclase-activating peptide Baseline + 8 weeks + 10 months Level (picograms per milliliter in plasma and cerebrospinal fluid) of Pituitary adenylate cyclase-activating peptide (PACAP)
Calcitonin Gene Related Peptide Baseline + 8 weeks + 10 months Calcitonin Gene Related Peptide (CGRP) level pg/mL (picograms per milliliter in plasma and cerebrospinal fluid)
Change in bone marker (CTX) Baseline + 8 weeks + 10 months Change in carboxy-terminal collagen crosslinks (CTX) level (nanograms per liter)
Change in bone marker (PiNP) baseline + 8 weeks + 10 months Change in procollagen type I N-propeptide (PiNP) level (micrograms per liter) compared to baseline
Regional bone density Baseline + 8 weeks + 10 months 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
Androgen metabolism_1 Baseline + 8 weeks + 10 months Ratio between Etiocholanolone and Androsterone (ng/mg) in 24-hour urine
Androgen metabolism_2 Baseline + 8 weeks + 10 months Ratio between 5-alpha-tetrahydrocortisol (5a-THF) and tetrahydrocortisol (THF) in 24-hour urine
Androgen metabolism_3 Baseline + 8 weeks + 10 months Level of testosterone in 24-hour urine (ng/L)
Androgen metabolism_4 Baseline + 8 weeks + 10 months Level of 3-alpha-androstanediol in 24-hour urine (nmol/L)
Androgen metabolism_5 Baseline + 8 weeks + 10 months Level of 11-oxygenated androgens (11-OHA4) (pg/L) in 24-hour urine
Intrathecal Semaglutide 10 months Level of semaglutide in cerebrospinal fluid (picomol/L)
Ammoniaemia_1 Baseline + 8 weeks + 10 months Levels of plasma ammonium (umol/L)
Ammoniaemia_2 Baseline + 8 weeks + 10 months Correlation between plasma ammonium (umol/L) and presence of fatty liver disease as indicated by liver ultrasonography
Ketosis 8 weeks + 10 months Proportion of patients in ketosis measured by urine stix
Change in metabolic parameters 8 weeks + 10 months Change in glycated hemoglobin (mmol/mol) compared to baseline
Trial Locations
- Locations (2)
Danish Headache Center, Department of Neurology, Rigshospitalet
🇩🇰Glostrup, Denmark
Headache clinic, Department of Neurology, Odense University Hospital
🇩🇰Odense, Denmark