Glucagon-like Peptide-1 Receptor (GLP-1R) Analogue Assisted Rapid Weight Loss Program As Treatment of Idiopathic Intracranial Hypertension
试验速览
- 阶段
- 4 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 50
- 试验地点
- 2
- 主要终点
- Weight
研究概览
简要总结
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)
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Confirmed new onset definite IIH with papilledema and lumbar opening pressure ≥25 cm cerebrospinal fluid according to Friedmann diagnostic criteria
- •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
排除标准
- •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
研究组 & 干预措施
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
干预措施: Semaglutide (Drug)
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
干预措施: Very Low Calorie Diet (Dietary Supplement)
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
干预措施: Dietician counselling (Behavioral)
Standard care (dietician)
Standard weight loss intervention Counselling by dietician Standard medical treatment of intracranial hypertension
干预措施: Dietician counselling (Behavioral)
结局指标
主要结局
Weight
时间窗: 8 weeks
Weight change (%)
Intracranial pressure
时间窗: 8 weeks
Change in lumbar opening pressure (%)
次要结局
- Weight(10 months)
- Remission(8 weeks + 10 months)
- Change in fat mass(8 weeks + 10 months)
- Change in Papilledema(8 weeks + 10 months)
- Total fat mass(Baseline + 8 weeks + 10 months)
- Feasibility(8 weeks + 10 months)
- Need of intracranial pressure-lowering medication_1(8 weeks + 10 months)
- Fatty liver prevalence(Baseline + 8 weeks + 10 months)
- Monthly headache days(Baseline + 8 weeks + 10 months)
- Headche severity(Baseline + 8 weeks + 10 months)
- Intracranial Pressure(10 months)
- Quality of Life(8 weeks + 10 months)
- Peripapillary capillary density(Baseline + 8 weeks + 10 months)
- Peripapillary artery-to-venule ratio(Baseline + 8 weeks + 10 months)
- Truncal fat(Baseline + 8 weeks + 10 months)
- Headache burden measured by HURT questionnaire(8 weeks + 10 months)
- Visual fields(8 weeks + 10 months)
- EDI-OCT(8 weeks + 10 months)
- Optic disc elevation(Baseline + 8 weeks + 10 months)
- Headache medication - Acute analgesic use(Baseline + 8 weeks + 10 months)
- Headache medication - preventive medication(Baseline + 8 weeks + 10 months)
- Optic nerve sheath diameter(Baseline + 8 weeks + 10 months)
- Android-gynoid-ratio(Baseline + 8 weeks and 10 months)
- Adverse events(8 weeks + 10 months)
- Need of intracranial pressure-lowering medication_2(Baseline + 8 weeks + 10 months)
- Insulin like-Growth-Factor-1(Baseline)
- Insulinlike Growth Factor Binding Protein-3(Baseline)
- Growth hormone(Baseline)
- Lutropin(Baseline)
- Follitropin(Baseline)
- Testosteron(Baseline)
- Estradiol(Baseline)
- Sex-Hormone Binding Globulin(Baseline)
- Androgen metabolism_3(Baseline + 8 weeks + 10 months)
- Androgen metabolism_4(Baseline + 8 weeks + 10 months)
- Anti-Müllerian Hormone(Baseline)
- Dehydroepiandrosterone(Baseline)
- Androstenedion(Baseline)
- 17-hydroxyprogesterone (mg/d)(Baseline)
- Cortisol 0 min(Baseline)
- Cortisol 30 min(Baseline)
- Pituitary adenylate cyclase-activating peptide (PACAP) Pituitary adenylate cyclase-activating peptide Pituitary adenylate cyclase-activating peptide(Baseline + 8 weeks + 10 months)
- Calcitonin Gene Related Peptide(Baseline + 8 weeks + 10 months)
- Change in bone marker (CTX)(Baseline + 8 weeks + 10 months)
- Change in bone marker (PiNP)(baseline + 8 weeks + 10 months)
- Regional bone density(Baseline + 8 weeks + 10 months)
- Androgen metabolism_1(Baseline + 8 weeks + 10 months)
- Androgen metabolism_2(Baseline + 8 weeks + 10 months)
- Androgen metabolism_5(Baseline + 8 weeks + 10 months)
- Intrathecal Semaglutide(10 months)
- Ammoniaemia_1(Baseline + 8 weeks + 10 months)
- Ammoniaemia_2(Baseline + 8 weeks + 10 months)
- Ketosis(8 weeks + 10 months)
- Change in metabolic parameters(8 weeks + 10 months)
研究者
Rigmor Højland Jensen
Professor in Neurology
Danish Headache Center