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Completed

NCT Number: 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

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)

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Key information

Conditions

Idiopathic Intracranial Hypertension Body Weight Body Weight Changes Brain Diseases Central Nervous System Diseases Cranial Nerve Diseases Eye Diseases Intracranial Hypertension Intracranial Pressure Nervous System Diseases Nutrition Disorders Nutritional and Metabolic Diseases Obesity Optic Nerve Diseases Overnutrition Overweight Papilledema Pathological Conditions, Signs and Symptoms Pseudotumor Cerebri Pseudotumor Cerebri Syndrome Signs and Symptoms Weight Loss

Age range

18 year–65 year

Sex eligibility

Female

Study type

Interventional

Phase

Phase 4

Primary location

Headache clinic, Department of Neurology, Odense University Hospital, Odense, Denmark

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

semaglutide

Drug

Subcutaneous once-weekly injections of Semaglutide uptitrating to a maximum of 2.4 mg

Other names: Ozempic, Wegovy

Very Low Calorie Diet

Dietary Supplement

Very Low Calorie Diet (max 800 kcal/day) using Nupo Diet meal replacement products

Dietician counselling

Behavioral

Counselling by a dietician on weight loss through behavioural changes and life style intervention

Primary outcomes

  1. Weight

    Time frame: 8 weeks

    Weight change (%)

  2. Intracranial pressure

    Time frame: 8 weeks

    Change in lumbar opening pressure in cm cerebrospinal fluid measured by manometry

  3. Intracranial pressure

    Time frame: 8 weeks

    Change in lumbar opening pressure (%)

Secondary outcomes

  1. Weight

    Time frame: 10 months

    Weight change (%)

  2. Intracranial Pressure

    Time frame: 10 months

    Change in lumbar opening pressure in cm cerebrospinal fluid measured by manometry

  3. Intracranial Pressure

    Time frame: 10 months

    Change in lumbar opening pressure (%)

  4. Quality of Life

    Time frame: 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)

  5. Headache burden measured by HURT questionnaire

    Time frame: 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

  6. Change in Papilledema

    Time frame: 8 weeks + 10 months

    Change in Frisén Grade (0-5, 0 minimal, 5 worst)

  7. Visual fields

    Time frame: 8 weeks + 10 months

    Perimetric mean deviation (decibel) by Humphrey automated perimetry

  8. EDI-OCT

    Time frame: 8 weeks + 10 months

    Change in Papillary thickness (um) measured by Enhanced Depth Imaging Optical Coherence Tomography (EDI-OCT)

  9. Optic disc elevation

    Time frame: Baseline + 8 weeks + 10 months

    Optic disc elevation (mm) measured by transorbital ultrasonography, (average of 3 scans of each eye with papilledema)

  10. Remission

    Time frame: 8 weeks + 10 months

    Proportion of patients with abscence of papilledema with or without intracranial pressure <25 cm cerebrospinal fluid

  11. Change in fat mass

    Time frame: 8 weeks + 10 months

    Change in body fat percentage measured by Dual Energy X-ray Absorptiometry compared to baseline

  12. Total fat mass

    Time frame: Baseline + 8 weeks + 10 months

    Body fat percentage measured by Dual Energy X-ray Absorptiometry

  13. Feasibility

    Time frame: 8 weeks + 10 months

    Drop-out rate (proportion of patients withdrawing from participation)

  14. Need of intracranial pressure-lowering medication_1

    Time frame: 8 weeks + 10 months

    Dose (mg) of intracranial pressure-lowering medication needed (Acetazolamide, Topiramate, diuretics)

  15. Fatty liver prevalence

    Time frame: 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

  16. Monthly headache days

    Time frame: Baseline + 8 weeks + 10 months

    Number of days with headache for the past 30 days preceding visit

  17. Headche severity

    Time frame: Baseline + 8 weeks + 10 months

    Number of days with mild, moderate, and severy headache, respectively, in the past 30 days preceding visit

  18. Headache medication - Acute analgesic use

    Time frame: Baseline + 8 weeks + 10 months

    Number of days with need of acute analgesic treatment for headache

  19. Headache medication - preventive medication

    Time frame: Baseline + 8 weeks + 10 months

    Need of preventive medical treatment for headache

  20. Optic nerve sheath diameter

    Time frame: Baseline + 8 weeks + 10 months

    Optic nerve sheath diameter (mm) measured by transorbital ultrasonography (average of 3 scans of each eye with papilledema)

  21. Peripapillary capillary density

    Time frame: 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

  22. Peripapillary artery-to-venule ratio

    Time frame: Baseline + 8 weeks + 10 months

    Change in peripapillary artery-to-venule diameter ratio measured by confocal Scanning Laser Ophtalmoscopy

  23. Truncal fat

    Time frame: Baseline + 8 weeks + 10 months

    Change in percentage of truncal adiposity measured by Dual Energy X-ray Absorptiometry

  24. Android-gynoid-ratio

    Time frame: Baseline + 8 weeks and 10 months

    Change in ratio of Android versus gynoid fat percentage using Dual Energy X-ray Absorptiometry

  25. Adverse events

    Time frame: 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

  26. Need of intracranial pressure-lowering medication_2

    Time frame: Baseline + 8 weeks + 10 months

    Number of patients in need of any intracranial pressure-lowering drug (Acetazolamide, Topiramate, diuretics)

  27. Insulin like-Growth-Factor-1

    Time frame: Baseline

    Level of Insulin like-Growth-Factor-1 in serum (ug/L) in women not taking estrogen-containing contraceptives.

  28. Insulinlike Growth Factor Binding Protein-3

    Time frame: Baseline

    Level of Insulinlike Growth Factor Binding Protein-3 in serum (ug/L) in women not taking estrogen-containing contraceptives.

  29. Growth hormone

    Time frame: Baseline

    Level of growth hormone in serum ug(L) in women not taking estrogen-containing contraceptives.

  30. Lutropin

    Time frame: Baseline

    Level of Lutropin in serum (IU/L) in women not taking estrogen-containing contraceptives.

  31. Follitropin

    Time frame: Baseline

    Level of Follitropin in serum (IU/L) in women not taking estrogen-containing contraceptives.

  32. Testosteron

    Time frame: Baseline

    Level of testosteron in serum (nmol/L) in women not taking estrogen-containing contraceptives.

  33. Estradiol

    Time frame: Baseline

    Level of estradiol in serum (nmol/L) in women not taking estrogen-containing contraceptives.

  34. Sex-Hormone Binding Globulin

    Time frame: Baseline

    Level of Sex-Hormone Binding Globulin in serum (nmol/L) in women not taking estrogen-containing contraceptives.

  35. Anti-Müllerian Hormone

    Time frame: Baseline

    Level of Anti-Müllerian Hormone (pmol/L) in serum in women not taking estrogen-containing contraceptives.

  36. Dehydroepiandrosterone

    Time frame: Baseline

    Level of Dehydroepiandrosterone (DHEAS) in serum (umol/L) in women not taking estrogen-containing contraceptives.

  37. Androstenedion

    Time frame: Baseline

    Level of androstenedion (nmol/L) in serum in women not taking estrogen-containing contraceptives.

  38. 17-hydroxyprogesterone (mg/d)

    Time frame: Baseline

    Level of 17-hydroxyprogesterone (mg/d) in serum in women not taking estrogen-containing contraceptives.

  39. Cortisol 0 min

    Time frame: Baseline

    Level of cortisol (nmol/L) in serum in women not taking estrogen-containing contraceptives.

  40. Cortisol 30 min

    Time frame: Baseline

    Level of cortisol (nmol/L) in serum 30 minutes after stimulation with 0,25 mg SynACHTen in women not taking estrogen-containing contraceptives.

  41. Pituitary adenylate cyclase-activating peptide (PACAP) Pituitary adenylate cyclase-activating peptide Pituitary adenylate cyclase-activating peptide

    Time frame: Baseline + 8 weeks + 10 months

    Level (picograms per milliliter in plasma and cerebrospinal fluid) of Pituitary adenylate cyclase-activating peptide (PACAP)

  42. Calcitonin Gene Related Peptide

    Time frame: Baseline + 8 weeks + 10 months

    Calcitonin Gene Related Peptide (CGRP) level pg/mL (picograms per milliliter in plasma and cerebrospinal fluid)

  43. Change in bone marker (CTX)

    Time frame: Baseline + 8 weeks + 10 months

    Change in carboxy-terminal collagen crosslinks (CTX) level (nanograms per liter)

  44. Change in bone marker (PiNP)

    Time frame: baseline + 8 weeks + 10 months

    Change in procollagen type I N-propeptide (PiNP) level (micrograms per liter) compared to baseline

  45. Regional bone density

    Time frame: 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

  46. Androgen metabolism_1

    Time frame: Baseline + 8 weeks + 10 months

    Ratio between Etiocholanolone and Androsterone (ng/mg) in 24-hour urine

  47. Androgen metabolism_2

    Time frame: Baseline + 8 weeks + 10 months

    Ratio between 5-alpha-tetrahydrocortisol (5a-THF) and tetrahydrocortisol (THF) in 24-hour urine

  48. Androgen metabolism_3

    Time frame: Baseline + 8 weeks + 10 months

    Level of testosterone in 24-hour urine (ng/L)

  49. Androgen metabolism_4

    Time frame: Baseline + 8 weeks + 10 months

    Level of 3-alpha-androstanediol in 24-hour urine (nmol/L)

  50. Androgen metabolism_5

    Time frame: Baseline + 8 weeks + 10 months

    Level of 11-oxygenated androgens (11-OHA4) (pg/L) in 24-hour urine

  51. Intrathecal Semaglutide

    Time frame: 10 months

    Level of semaglutide in cerebrospinal fluid (picomol/L)

  52. Ammoniaemia_1

    Time frame: Baseline + 8 weeks + 10 months

    Levels of plasma ammonium (umol/L)

  53. Ammoniaemia_2

    Time frame: Baseline + 8 weeks + 10 months

    Correlation between plasma ammonium (umol/L) and presence of fatty liver disease as indicated by liver ultrasonography

  54. Ketosis

    Time frame: 8 weeks + 10 months

    Proportion of patients in ketosis measured by urine stix

  55. Change in metabolic parameters

    Time frame: 8 weeks + 10 months

    Change in Homeostatic Model for Insulin Resistance (HOMA2IR) compared to baseline

  56. Change in metabolic parameters

    Time frame: 8 weeks + 10 months

    Change in glycated hemoglobin (mmol/mol) compared to baseline

Other outcomes

  1. Omics

    Time frame: Baseline + 8 weeks + 10 months

    Metabolomic and proteomic profile, exploratory analyses

Sponsors and collaborators

Lead sponsor

Rigmor Højland Jensen

Other

Collaborators

  • Odense University Hospital
  • Rigshospitalet, Denmark
  • University of Copenhagen

Registry information

Official study title

Glucagon-like Peptide-1 Receptor (GLP-1R) Analogue Assisted Rapid Weight Loss Program as Treatment of Idiopathic Intracranial Hypertension

Acronym: IIH:DUAL

Important dates

Study start
2022
Primary completion
2025
Study completion
2025
First posted
Sep 7, 2023
Registry last updated
Feb 27, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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