IIH Pressure - a new treatment for raised brain pressure in Idiopathic Intracranial Hypertension
| ISRCTN | ISRCTN12678718 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN12678718 |
| Secondary identifying numbers | CPMS 34681 |
- Submission date
- 19/06/2017
- Registration date
- 18/07/2017
- Last edited
- 05/08/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Nervous System Diseases
Plain English Summary
Background and study aims
Idiopathic intracranial hypertension (IIH) is a condition of unknown cause. The condition is causes raised pressure in the brain and can cause 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 and cause blindness. 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 and few treatments in general are available for raised brain pressure. Gut neuro-peptides are a group of hormones released by the gut with specific actions in the central nervous system. GLP-1 is a hormone that has known actions in the kidney to reduce blood pressure. Preliminary work has shown this mechanism to be similar to that regulating fluid secretion in the brain. Further preliminary work has shown that GLP-1 reduces intra-cranial pressure in animal models. GLP-1 drugs are currently used to treat diabetes and aid weight loss. The aim of this study is to investigate the effects of the GLP-1 drug, exenatide, on intra-cranial pressure as well as evaluate the effect of five common medications on intra-cranial pressure.
Who can participate?
Females aged 18 to 60 years old who are diagnosed with IIH.
What does the study involve?
This study has two parts. The first part of the study includes participants having telemetric intra-cranial pressure sensors fitted. Participants are randomised to one of two groups. Those in the first group receive exenatide through skin injections twice daily for 12 weeks. Those in the second group receive a placebo (a dummy medication). This is given through skin injections twice daily for 12 weeks. Participants are followed up at two and 12 weeks with intracranial pressure recording (ICP) which is a non-invasive monitor, as well as blood tests, headaches scores and cognitive (mental) testing). At 12 weeks, participants are assessed for their quality of life, and clinical measurements. The second part of the study randomly allocates participants to receiving one of five medications for two weeks (with one week washout between them).
What are the possible benefits and risks of participating?
Participants may benefit from receiving brain pressure monitors which is non-invasive and can improve monitoring. Participants may benefit from improvements in their conditions depending on the medication they receive. Participants may benefit from increased clinical observation during the study period as well as opportunities to improve their understanding of their condition. There is a small risk from using anesthesia as well as small risks from the procedure of bleeding near the brain, infection or seizures after the procedure. There is a small risk that the device could fail which requires another surgery to remove the device.There is a risk of nausea due to the medication. There are rare reports of pancreatitis associated with the medication.
Where is the study run from?
This study is being run by the University of Birmingham (UK) and takes place in six health centres/hospitals in the UK.
When is the study starting and how long is it expected to run for?
June 2015 to July 2019
Who is funding the study?
Ministry of Defence (UK)
Who is the main contact?
Mr James Mitchell
Contact information
Public
Neurometabolism
Institute of Systems and Metabolism Research
College of Medical and Dental Sciences
University of Birmingham
Edgbaston
B15 2TT
United Kingdom
 ORCID ID |
0000-0001-6785-9352 |
|---|
Study information
| Study design | Randomized; Interventional; Design type: Treatment, Drug |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| Scientific title | The acute and chronic effects of gut neuropeptides on intracranial pressure regulation |
| Study acronym | IIH Pressure |
| Study hypothesis | Exenatide modulates fluid secretion and inflammatory biomarkers in the central nervous system following acute administration. |
| Ethics approval(s) | West Midlands Research Ethics Committee - Solihull, 29/06/2017, ref: 17/WM/0179 |
| Condition | Idiopathic intracranial hypertension |
| Intervention | The main part of the trial has two arms, active treatment and placebo. The second part of the trial is single arm and open to all participants on the main trial. First part of the study: The randomisation process for the main trial is by computer generated list. The active treatment arm receives a single bolus of the study drug, exenatide at baseline. The dose is 20 mcg Exenatide (Byetta) via subcutaneous injection. Following the baseline day all active arm participants receive 10 mcg Exenatide (Byetta) via subcutaneous injection twice daily and self administer. The duration of treatment is 12 weeks. Follow-up takes place at 2 weeks and 12 weeks. The placebo arm receives a single bolus of Normal Saline Placebo at baseline. The dose includes 1 mL via subcutaneous injection. Following the baseline day all placebo arm participants receive 0.5 mL Normal Saline via subcutaneous injection twice daily and will self administer. The duration of treatment will be 12 weeks. Follow-up is done at two weeks and 12 weeks. Follow up is done at two and 12 weeks where participants undergo Intracranial pressure (ICP) recording, IOP, blood sampling, OCT, headache scores and cognitive testing. Additionally, at 12 weeks participants also undergo clinical measurements, quality of life questionnaires, and DEXA scan. Second part of the study: This part of the study is a single arm sequential, open label design. All participants receive all medications in random order. The duration of treatment is two weeks, week one is a titration week where necessary. There will be a minimum one week washout between rounds. Follow-up is by visit at two weeks. The medications for this part of the study are: Acetazolomide: Patients take 500 mg BD PO immediate release for 7 days, followed by 1g BD for 7 days. Spironolactone: Participants take 100 mg OD PO for 7 days, followed by 200 mg OD for 7 days. Amiloride: Participants take 10 mg OD PO for 14 days. Furosemide: Patients take 40 mg OD PO for 7 days, followed by 80 mg OD for 7 days. Topiramate: Participants take 25mg BD PO for 4 days, followed by 25 mg mane/50 mg nocte for 3 days followed by 50 mg BD for 7 days. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Not Specified |
| Drug / device / biological / vaccine name(s) | Exenatide, acetazolomide, spironolactone, amiloride, furosemide, topiramate |
| Primary outcome measure | 1. Change in Intracranial pressure (ICP) measured by telemetric ICP catheter between baseline and 24 hours post drug administration 2. Change in ICP measured by telemetric ICP catheter between baseline and end of trial visit 3. Change in ICP measured by telemetric ICP catheter between baseline and 2.5 hours post administration |
| Secondary outcome measures | 1. Biological effects of exenatide measured using blood tests at 24 h, 2 and 12 weeks 2. Headaches measured using severity scores at 24 h, 2 and 12 weeks 3. Quality of life measured using SF-36 at baseline and 12 weeks 4. CSF exenatide levels measured by assay at two and a half, six and 11 hours |
| Overall study start date | 01/06/2015 |
| Overall study end date | 31/07/2019 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 60 Years |
| Sex | Female |
| Target number of participants | Planned Sample Size: 16; UK Sample Size: 16 |
| Total final enrolment | 15 |
| Participant inclusion criteria | 1. Female 2. Aged 18-60 years old 3. Diagnosed with IIH by the modified Dandy criteria 4. Active disease (papilloedema Frisen grade greater than 1) 5. Significantly raised ICP (greater than 25cm CSF) 6. No evidence of venous sinus thrombosis (documented normal MR Venogram of CT Venogram) 6. Able to provide informed consent |
| Participant exclusion criteria | 1. Aged less than 18 or older than 60 years 2. Pregnant or trying to conceive 3. Significant co-morbidity, such that in the opinion of the investigator it would not be in the participant’s best interest to participate in the trial 4. Addison’s or Cushing’s disease 5. Functioning CSF shunt/stent or optic nerve sheath fenestration 6. Currently using GLP-1 agonist or DPP-4 inhibitor 7. Surgical contra-indication 8. Concomitant therapy with acetazolomide, topiramate or diuretics (this can be discontinued 1 month prior to enrolment) 9. Inability to give informed consent e.g. due to cognitive impairment |
| Recruitment start date | 31/07/2017 |
| Recruitment end date | 31/07/2018 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centres
Edgbaston
Birmingham
B15 2WG
United Kingdom
West Bromwich
B71 4HJ
United Kingdom
Gloucestershire
Gloucester
GL1 3NN
United Kingdom
Leicester
LE5 4PW
United Kingdom
Sheffield
S10 2JF
United Kingdom
Coventry
CV2 2DX
United Kingdom
Sponsor information
Hospital/treatment centre
Birmingham
Birmingham
B15 2TT
England
United Kingdom
"ROR" |
https://ror.org/03angcq70 |
|---|
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- MOD
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 31/07/2019 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | Planned publication in a high impact, peer-reviewed journal, intent to publish by July 2019. |
| IPD sharing plan | The current data sharing plans for the current study are unknown and will be made available at a later date. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Other publications | Evaluation of telemetric intracranial pressure monitoring | 01/11/2022 | 03/11/2022 | Yes | No |
| Preprint results | Exenatide results | 06/09/2022 | 07/11/2022 | No | No |
| HRA research summary | 28/06/2023 | No | No | ||
| Abstract results | 07/12/2022 | 05/08/2024 | No | No | |
| Other publications | 01/12/2020 | 05/08/2024 | Yes | No | |
| Other publications | Sub-study | 22/11/2023 | 05/08/2024 | Yes | No |
Editorial Notes
05/08/2024: Publication references and abstract added.
07/11/2022: Preprint reference added.
03/11/2022: Publication reference and total final enrolment added.
11/08/2017: Internal review.
