Tirzepatide in Idiopathic Intracranial Hypertension Trial

Not Applicable

Not yet recruiting

• Conditions: Idiopathic Intracranial Hypertension (IIH)
• Interventions: Drug: Tirzepatide; Drug: Tirzepatide Placebo

• Registration Number: NCT07191873
• Lead Sponsor: Duke University

Brief Summary

This will be a randomized, double-blind, parallel, placebo-controlled trial of 60 participants. The primary analysis will be a statistical comparison of the estimates of the mean difference in the 12-month change in intracranial pressure (ICP) between participants assigned to the tirzepatide and Placebo arms in 1:1 randomization using the intention-to-treat (ITT) population. Hypothesis testing will be performed using analysis of covariance (ANCOVA), with the treatment indicator as the independent variable and the 12-month change in ICP as the dependent variable. Models will include baseline ICP as a covariate. This primary endpoint will use a significance level of 0.05 to declare significance.

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-09
• Study Start: 2025-09-01
• Study First Submitted: 2025-09-17
• Study First Submitted QC: 2025-09-17
• Last Update Submitted: 2025-09-17
• Study First Posted: 2025-09-25
• Last Update Posted: 2025-09-25
• Primary Completion: 2027-07
• Study Completion: 2027-09-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

1. Signs and symptoms of increased intracranial pressure:

   1. headaches, tinnitus, visual obscurations, papilledema;
   2. absence of localizing findings on neurological examination (except for VI nerve palsy);
   3. no secondary causes identified on imaging, e.g., hydrocephalus, space- occupying lesion;
   4. elevated lumbar puncture (LP) opening pressure (OP) ≥25 cm H2O in lateral decubitus position with legs extended (>= (≥ 20cm H2O if one of the following is present: pulse synchronous tinnitus, abducens palsy, Frisen grade II papilledema, transverse venous sinus stenosis, partially empty sella or enlarged optic nerve sheath on magnetic resonance imaging (MRI);
   5. the patient is awake and alert.

2. BMI ≥30 kg/m2

3. Age 18-60 years of age

4. Unilateral or bilateral papilledema

5. Able to provide informed consent

6. Women of child-bearing age must use birth control (non-oral contraceptive method or add a barrier method of contraception).

Exclusion Criteria

1. Previous bariatric surgery
2. Prior intervention for high ICP including optic nerve sheath fenestration (ONSF), venous stenting and/or shunting
3. Taking another GLP-1 agonist, another drug that can interfere with the GLP-1 agonist, or any other anti-obesity medication
4. History of pancreatitis, personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2 (MEN2), history of gallbladder disease, ulcerative colitis, Crohn's disease, or history of hypersensitivity reaction in response to the drug
5. Pregnancy or planning a pregnancy in the next 12 months or currently breastfeeding
6. Other disorders causing visual loss and/or anomalous optic nerve
7. Taking another medication to lower ICP in IIH (if previously taking another medication for ICP must be off this medication for at least 30 days prior to enrollment)
8. No change in headache medications in the past 60 days
9. Venous sinus thrombosis on magnetic resonance venography (MRV)
10. Papilledema Frisen Grade III, IV or fulminant IIH
11. Mean perimetric deviation ≤ -7 dB
12. CSF contents outside of normal limits
13. Uncontrolled hypertension (≥140mmHg/90 mmHg)
14. Anemia (hemoglobin [Hgb] ≤ 8.0g/dL)
15. Diagnosed sleep apnea with continuous positive airway pressure (CPAP) use
16. Exposure to a drug, substance, or disorder that has been associated with elevation of intracranial pressure within 2 months of diagnosis such as lithium, vitamin A, various cyclines
17. eGFR < 30 ml/min/1.73m2
18. Type II diabetes

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Tirzepatide	Tirzepatide	Participants receive Tirzepatide weekly on the following dose schedule for a year: Dosage Treatment time 2.5mg/0.5mL: Month 1 (4 Weeks) 5mg/0.5mL: Month 2 (4 Weeks) 7.5mg/0.5mL: Month 3 (4 Weeks) 10mg/0.5mL: Month 4 (4 Weeks) 12.5mg/0.5mL: Month 5-6 15mg/0.5 mL: Month 7-12
Placebo	Tirzepatide Placebo	Participants receive Tirzepatide Placebo weekly on the following dose schedule for a year: Dosage Treatment time 2.5mg/0.5mL: Month 1 (4 Weeks) 5mg/0.5mL: Month 2 (4 Weeks) 7.5mg/0.5mL: Month 3 (4 Weeks) 10mg/0.5mL: Month 4 (4 Weeks) 12.5mg/0.5mL: Month 5-6 15mg/0.5 mL: Month 7-12

Primary Outcome Measures

Name	Time	Method
Change in intracranial pressure in Idiopathic Intracranial Hypertension (IIH) patients	From enrollment to end of treatment at 12 months	Assessed by opening pressure via lumbar puncture (LP) in the left lateral decubitus position and measured in cm H2O.

Secondary Outcome Measures

Name	Time	Method
Retinal Nerve Fiber Layer (RNFL) Thickness on optical coherence tomograhy (OCT)	From enrollment to end of treatment at 12 months	Mean change in RNFL thickness
Change in Frisen papilledema grade on fundus photography	From enrollment to the end of treatment at 12 months	The Frisen scale ranges from 0 (normal optic disc) to 5 (severe degree of edema).
Change in perimetric mean deviation	From enrollment to end of treatment at 12 months	Perimetric Mean Deviation (MD) is a key visual field index that represents the average point-by-point difference between a patient's visual field and the normal, age-matched expected visual field.

Trial Locations

Locations (1)

Duke University Medical Center; 🇺🇸 Durham, North Carolina, United States