Tirzepatide in Idiopathic Intracranial Hypertension Trial (TIIHT)

Duke University

Status and phase: Not yet enrolling; Phase 4

Conditions: Idiopathic Intracranial Hypertension (IIH)

Treatments: Drug: Tirzepatide Placebo; Drug: Tirzepatide

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT07191873

Pro00117470

Details and patient eligibility

About

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.

Enrollment: 60 estimated patients

Sex: All

Ages: 18 to 60 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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60 participants in 2 patient groups, including a placebo group

Tirzepatide

Active Comparator group

Description:

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

Treatment:

Drug: Tirzepatide

Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Tirzepatide Placebo