Tirzepatide in Idiopathic Intracranial Hypertension Trial

NCT07191873 | Not Yet Recruiting Phase 4 FDA Drug

• 1 other identifier: Pro00117470
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

Idiopathic Intracranial Hypertension (IIH)

Keywords

IIH; BMI; Eye Pressure; Headache

Outcome Measures

Primary Outcomes (1)

• Change in intracranial pressure in Idiopathic Intracranial Hypertension (IIH) patients

  Assessed by opening pressure via lumbar puncture (LP) in the left lateral decubitus position and measured in cm H2O.

  From enrollment to end of treatment at 12 months

Secondary Outcomes (3)

• Retinal Nerve Fiber Layer (RNFL) Thickness on optical coherence tomograhy (OCT)

  From enrollment to end of treatment at 12 months

• Change in Frisen papilledema grade on fundus photography

  From enrollment to the end of treatment at 12 months

• Change in perimetric mean deviation

  From enrollment to end of treatment at 12 months

Study Arms (2)

Tirzepatide

ACTIVE COMPARATOR

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

Drug: Tirzepatide

Placebo

PLACEBO COMPARATOR

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

Drug: Tirzepatide Placebo

Interventions

Tirzepatide DRUG

Dosage Treatment time 2.5mg/0.5mL: 4 Weeks 5mg/0.5mL: 4 Weeks 7.5mg/0.5mL: 4 Weeks 10mg/0.5mL: 4 Weeks 12.5mg/0.5mL: 4 weeks 15mg/0.5 mL: 7 Months

Tirzepatide

Tirzepatide Placebo DRUG

Dosage Treatment time 2.5mg/0.5mL: 4 Weeks 5mg/0.5mL: 4 Weeks 7.5mg/0.5mL: 4 Weeks 10mg/0.5mL: 4 Weeks 12.5mg/0.5mL: 4 weeks 15mg/0.5 mL: 7 Months

Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Signs and symptoms of increased intracranial pressure:
• headaches, tinnitus, visual obscurations, papilledema;
• absence of localizing findings on neurological examination (except for VI nerve palsy);
• no secondary causes identified on imaging, e.g., hydrocephalus, space- occupying lesion;
• 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);
• the patient is awake and alert.
• BMI ≥30 kg/m2
• Age 18-60 years of age
• Unilateral or bilateral papilledema
• Able to provide informed consent
• Women of child-bearing age must use birth control (non-oral contraceptive method or add a barrier method of contraception).

You may not qualify if:

• Previous bariatric surgery
• Prior intervention for high ICP including optic nerve sheath fenestration (ONSF), venous stenting and/or shunting
• Taking another GLP-1 agonist, another drug that can interfere with the GLP-1 agonist, or any other anti-obesity medication
• 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
• Pregnancy or planning a pregnancy in the next 12 months or currently breastfeeding
• Other disorders causing visual loss and/or anomalous optic nerve
• 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)
• No change in headache medications in the past 60 days
• Venous sinus thrombosis on magnetic resonance venography (MRV)
• Papilledema Frisen Grade III, IV or fulminant IIH
• Mean perimetric deviation ≤ -7 dB
• CSF contents outside of normal limits
• Uncontrolled hypertension (≥140mmHg/90 mmHg)
• Anemia (hemoglobin \[Hgb\] ≤ 8.0g/dL)
• Diagnosed sleep apnea with continuous positive airway pressure (CPAP) use

Sponsors & Collaborators

• Duke University: lead
• Eli Lilly and Company: collaborator

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Related Publications (5)

• Spitze A, Lam P, Al-Zubidi N, Yalamanchili S, Lee AG. Controversies: Optic nerve sheath fenestration versus shunt placement for the treatment of idiopathic intracranial hypertension. Indian J Ophthalmol. 2014 Oct;62(10):1015-21. doi: 10.4103/0301-4738.146012.

  PMID: 25449938 BACKGROUND

• Chen J, Wall M. Epidemiology and risk factors for idiopathic intracranial hypertension. Int Ophthalmol Clin. 2014 Winter;54(1):1-11. doi: 10.1097/IIO.0b013e3182aabf11. No abstract available.

  PMID: 24296367 BACKGROUND

• Mollan SP, Ali F, Hassan-Smith G, Botfield H, Friedman DI, Sinclair AJ. Evolving evidence in adult idiopathic intracranial hypertension: pathophysiology and management. J Neurol Neurosurg Psychiatry. 2016 Sep;87(9):982-92. doi: 10.1136/jnnp-2015-311302. Epub 2016 Feb 17.

  PMID: 26888960 BACKGROUND

• Miah L, Strafford H, Fonferko-Shadrach B, Hollinghurst J, Sawhney IMS, Hadjikoutis S, Rees MI, Powell R, Lacey A, Pickrell WO. Incidence, Prevalence, and Health Care Outcomes in Idiopathic Intracranial Hypertension: A Population Study. Neurology. 2021 Feb 22;96(8):e1251-e1261. doi: 10.1212/WNL.0000000000011463.

  PMID: 33472926 BACKGROUND

• Mollan SP, Aguiar M, Evison F, Frew E, Sinclair AJ. The expanding burden of idiopathic intracranial hypertension. Eye (Lond). 2019 Mar;33(3):478-485. doi: 10.1038/s41433-018-0238-5. Epub 2018 Oct 24.

  PMID: 30356129 BACKGROUND

MeSH Terms

Conditions

Pseudotumor Cerebri; Headache

Interventions

Tirzepatide

Condition Hierarchy (Ancestors)

Intracranial Hypertension; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide Receptors; Receptors, G-Protein-Coupled; Receptors, Cell Surface; Membrane Proteins; Proteins; Amino Acids, Peptides, and Proteins; Receptors, Gastrointestinal Hormone; Receptors, Peptide

Study Officials

• Alexa N Bramall, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Alexa N Bramall, MD

CONTACT

919-660-1754; alexa.bramall@duke.edu

Beth Perry, RN

CONTACT

919-681-2695; beth.perry@duke.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 17, 2025
• First Posted: September 25, 2025
• Study Start: February 1, 2026
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2028
• Last Updated: November 14, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)