An RCT of Bariatric Surgery vs a Community Weight Loss Programme for the Sustained Treatment of IIH (IIH:WT)

A Randomised Controlled Trial of Bariatric Surgery Versus a Community Weight Loss Programme for the Sustained Treatment of Idiopathic Intracranial Hypertension: the IIH:WT Trial

Idiopathic intracranial hypertension (IIH) is a condition with an unknown cause or causes. The condition is associated with raised pressure in the brain and can cause disabling daily headaches and loss of sight, which can be permanent. The raised brain pressure squashes the nerves supplying the eye (also known as papilloedema) and this can affect vision. Over 90% of patients with IIH are overweight and weight loss is the most effective treatment. Other treatments for IIH have very little current evidence to support their use.

Weight loss is difficult to maintain. This trial aims to compare two methods of weight loss, bariatric surgery and the most effective dietary programme commonly available, Weight Watchers, to see which offers the most effective sustainable treatment for IIH. Bariatric surgery is recommended by the NICE clinical guidelines for patients with a Body Mass Index (BMI) of over 40, or over 35 with a co-morbidity. Women suffering from IIH have a BMI on average around 38 and IIH is not recognised as a co-morbidity for bariatric surgery.

This trial will recruit 64 women with IIH from Neurology and Ophthalmology clinics in UK NHS Trusts. They will be randomised and 32 participants will be allocated to the dietetic intervention arm, and be enrolled in their local Weight Watchers group. 32 participants will be allocated to the bariatric surgery arm, and will be referred to their local bariatric surgery pathway to receive bariatric surgery. Both groups of participants will be allocated to a treatment arm which is proven to bring about weight loss.

Participants will then be followed up for five years, with the most important measurement being their brain pressure after one year of being in the trial.

A further 20 obese women who don't suffer from IIH will be recruited to compare the baseline symptoms and biomarkers of those with IIH; they will take no further part in the study. 5 further healthy individuals will be scanned twice in an MRI test group to validate the MRI scan sequence to be used in the trial.

Study Overview

• Status: Unknown
• Conditions: Idiopathic Intracranial Hypertension
• Intervention / Treatment: Behavioral: Dietetic intervention; Procedure: Bariatric surgery

• Study Type: Interventional
• Enrollment (Anticipated): 90
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • West Midlands
    • Birmingham, West Midlands, United Kingdom, B15 2TH
      • University Hospital Birmingham (Queen Elizabeth Hospital)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Female IIH patients aged between 18 and 55 years, diagnosed according to the modified Dandy criteria who have chronic (> 6 months duration), active disease (papilloedema [Frisen grade ≥ 1], significantly raised ICP > 25cmH2O) and no evidence of venous sinus thrombosis (magnetic resonance or CT imaging and venography as noted at diagnosis).
2. BMI >35kg/m2.
3. Tried other appropriate non-surgical treatments to lose weight but have not been able to achieve or maintain adequate, clinically beneficial weight loss for at least 6 months.
4. Able to give informed consent.

Exclusion Criteria:

1. Age less than 18 or older than 55 years.
2. Pregnant or planning to conceive during the first 18 months of the trial .
3. Significant co-morbidity, endocrinopathy or the use of hormone manipulating medication (excluding contraception and topical or inhaled steroids).
4. Undergone optic nerve sheath fenestration.
5. Definite indication for or contraindication against surgery or dieting.
6. Have a specific medical or psychiatric contraindication for surgery, including drug misuse, eating disorder or major depression (suicidal ideation, drug overdose or psychological admission in last 12 months).
7. Previous bariatric surgery.
8. Taken AZD4017 within the last four months .
9. Inability to give informed consent e.g. due to cognitive impairment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Dietetic Intervention; Participants randomised to the dietetic arm will be given vouchers at baseline, 3, 6 and 9 months that exempt them from paying for consecutive and specified weeks of their local Weight Watchers diet programme.	Behavioral: Dietetic intervention; Participants randomised to the dietetic arm will be given vouchers at baseline, 3, 6 and 9 months that exempt them from paying for consecutive and specified weeks of their local Weight Watchers.; Other Names: Weight Watchers
Experimental: Bariatric surgery; Patients randomised to the bariatric surgery arm will be referred to the bariatric surgery pathway and, if judged suitable according to the bariatric surgery clinic's screening processes, undergo bariatric surgery.	Procedure: Bariatric surgery; Participants randomised to the bariatric surgery arm of the trial will be referred to the surgery pathway according to NICE guidelines at Birmingham Heartlands Hospital (BHH), Heart of England NHS Foundation Trust.
No Intervention: Matched obese control group; To evaluate the baseline difference in ICP between IIH patients and a matched obese control cohort we will recruit 20 obese but otherwise healthy participants who will undergo the same baseline visit as the main trial participants and then exit the study.
No Intervention: MRI Test run; 5 patients will undergo double baseline MR scans to validate the novel MR sequences being used in the main trial.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intracranial Pressure	Change in Intracranial Pressure (ICP) between baseline and 12 months. ICP will be assessed using lumbar puncture (LP). To avoid the LP affecting the visual measures it will be performed after the visual tests have been completed. ICP will be recorded to the nearest whole number in cmH2O. Both opening and closing ICP will be recorded.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intracranial Pressure	Change in ICP between baseline and 24 and 60 months. ICP will be assessed using lumbar puncture (LP). To avoid the LP affecting the visual measures it will be performed after the visual tests have been completed. ICP will be recorded to the nearest whole number in cmH2O. Both opening and closing ICP will be recorded.	60 months
IIH symptoms	Change in reported IIH symptoms from 0 to 12 months (and at 3, 6, 24 and 60 months)	12 months
Visual function	Change in visual function from 0 to 12 months (and at 24 and 60 months). Assessments to be undertaken are the LogMAR (log of the minimum angle of resolution) chart to assess visual acuity, automated perimetry (Humphrey 24-2 central threshold) to measure the visual field mean deviation, an evaluation of contrast sensitivity and an Ishihara book to assess colour vision. The pupils will then be dilated using 1% tropicamide. Papilloedema will then be measured using spectral optical coherence tomography. Papilloedema will be further graded following fundus photographs. This will be done after all participants have reached the primary endpoint by two neuro-ophthalmologists blinded to trial treatment arm. The assessors will score the paired papilloedema images as better/same/worse as per the methodology described in a previous study. They will also assign a Frisen score to the images.	12 months
Papilloedema	Change in papilloedema from 0 to 12 months (and at 24 and 60 months)	12 months
Headache	Change in headache associated disability from 0 to 12 months (and at 24 and 60 months). Headache will be assessed by participant completed questionnaires. Participants will complete a daily headache diary in the week before assessments, which will evaluate the Headache Index score and use of analgesia (days/week). Headache associated disability will be evaluated using the Headache Impact Test-6 score (HIT 6). Severity and frequency of headaches will be assessed retrospectively using the Headache Index. Headache phenotype (according to criteria from the International Headache Society) will also be assessed.	12 months
Anthropometric measures	Change in anthropometric measures (e.g. waist, hip, fat mass) from 0 to 12 months (and at 24 and 60 months)	12 months
Quality of Life (EQ-5D-5L and SF-36)	Change in quality of life (participant reported) from 0 to 12 months (and at 24 and 60 months)	12 months
Referrals to CSF shunting procedures and optic nerve sheath fenestration	Difference in number of referrals to cerebrospinal fluid (CSF) shunting procedures and optic nerve sheath fenestration between treatment arms at 0 to 12 months (and at 24 and 60 months)	12 months
Health Economics	Health economics including cost-effectiveness at 12, 24 and 60 months.	12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biomarkers	Change in biomarkers from 0 to 12 (and 24 and 60) months	12 months
Matched control group comparison	Comparison between IIH patients and the matched control group at baseline with respect to biomarkers and ICP.	Baseline
MRI Test Run	Change in MR imaging over a double baseline period of healthy controls.	Baseline

Collaborators and Investigators

• Sponsor: University of Birmingham
• Collaborators: National Institute for Health Research, United Kingdom
• Investigators: Principal Investigator: Alexandra Sinclair, MBChB, University of Birmingham

Publications and helpful links

General Publications

• Mollan SP, Mitchell JL, Yiangou A, Ottridge RS, Alimajstorovic Z, Cartwright DM, Hickman SJ, Markey KA, Singhal R, Tahrani AA, Frew E, Brock K, Sinclair AJ. Association of Amount of Weight Lost After Bariatric Surgery With Intracranial Pressure in Women With Idiopathic Intracranial Hypertension. Neurology. 2022 Sep 13;99(11):e1090-e1099. doi: 10.1212/WNL.0000000000200839. Epub 2022 Jul 5.
• Mollan SP, Wakerley BR, Alimajstorovic Z, Mitchell J, Ottridge R, Yiangou A, Thaller M, Gupta A, Grech O, Lavery G, Brock K, Sinclair AJ. Intracranial pressure directly predicts headache morbidity in idiopathic intracranial hypertension. J Headache Pain. 2021 Oct 7;22(1):118. doi: 10.1186/s10194-021-01321-8.
• Yiangou A, Mitchell JL, Nicholls M, Chong YJ, Vijay V, Wakerley BR, Lavery GG, Tahrani AA, Mollan SP, Sinclair AJ. Obstructive sleep apnoea in women with idiopathic intracranial hypertension: a sub-study of the idiopathic intracranial hypertension weight randomised controlled trial (IIH: WT). J Neurol. 2022 Apr;269(4):1945-1956. doi: 10.1007/s00415-021-10700-9. Epub 2021 Aug 22.
• Mollan SP, Mitchell JL, Ottridge RS, Aguiar M, Yiangou A, Alimajstorovic Z, Cartwright DM, Grech O, Lavery GG, Westgate CSJ, Vijay V, Scotton W, Wakerley BR, Matthews TD, Ansons A, Hickman SJ, Benzimra J, Rick C, Singhal R, Tahrani AA, Brock K, Frew E, Sinclair AJ. Effectiveness of Bariatric Surgery vs Community Weight Management Intervention for the Treatment of Idiopathic Intracranial Hypertension: A Randomized Clinical Trial. JAMA Neurol. 2021 Jun 1;78(6):678-686. doi: 10.1001/jamaneurol.2021.0659. Erratum In: JAMA Neurol. 2021 Jul 1;78(7):882.
• Ottridge R, Mollan SP, Botfield H, Frew E, Ives NJ, Matthews T, Mitchell J, Rick C, Singhal R, Woolley R, Sinclair AJ. Randomised controlled trial of bariatric surgery versus a community weight loss programme for the sustained treatment of idiopathic intracranial hypertension: the Idiopathic Intracranial Hypertension Weight Trial (IIH:WT) protocol. BMJ Open. 2017 Sep 27;7(9):e017426. doi: 10.1136/bmjopen-2017-017426.

Study record dates

Study Major Dates

• Study Start (Actual): March 6, 2014
• Primary Completion (Actual): August 2, 2018
• Study Completion (Anticipated): August 2, 2022

Study Registration Dates

• First Submitted: April 22, 2014
• First Submitted That Met QC Criteria: April 24, 2014
• First Posted (Estimate): April 28, 2014

Study Record Updates

• Last Update Posted (Actual): November 5, 2020
• Last Update Submitted That Met QC Criteria: November 3, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: Bariatric surgery; Weight loss; IIH
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Body Weight; Body Weight Changes; Hypertension; Weight Loss; Intracranial Hypertension; Pseudotumor Cerebri
• Other Study ID Numbers: RG_12-089; CS-011-028 (Other Grant/Funding Number: NIHR); 14/WM/0011 (Other Identifier: Black Country Research Ethics Committee); ISRCTN40152829 (Registry Identifier: ISRCTN)