Condition category
Nervous System Diseases
Date applied
19/06/2017
Date assigned
18/07/2017
Last edited
11/08/2017
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

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 on 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

Trial website

Contact information

Type

Public

Primary contact

Mr James Mitchell

ORCID ID

http://orcid.org/0000-0001-6785-9352

Contact details

Neurometabolism
Institute of Systems and Metabolism Research
College of Medical and Dental Sciences
University of Birmingham
Edgbaston
B15 2TT
United Kingdom

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

34681

Study information

Scientific title

The acute and chronic effects of gut neuropeptides on intracranial pressure regulation

Acronym

IIH Pressure

Study hypothesis

Exenatide modulates fluid secretion and inflammatory biomarkers in the central nervous system following acute administration.

Ethics approval

West Midlands Research Ethics Committee - Solihull29/06/2017, ref: 17/WM/0179

Study design

Randomised; Interventional; Design type: Treatment, Drug

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Specialty: Neurological disorders, Primary sub-specialty: Other; UKCRC code/ Disease: Neurological/ Other disorders of the nervous system

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 20mcg Exenatide (Byetta) via subcutaneous injection. Following the baseline day all active arm participants receive 10mcg Exenatide (Byetta) via subcutaneous injection twice daily and self administer. The duration of treatment is 12 weeks. Follow-up takes place at two 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 pat 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 500mg BD PO immediate release for seven days, followed by 1g BD for seven days.
Spironolactone: Participants take 100mg OD PO for seven days, followed by 200mg OD for seven days.
Amiloride: Participants take 10mg OD PO for 14 days.
Furosemide: Patients take 40mg OD PO for seven days, followed by 80mg OD for seven days.
Topiramate: Participants take 25mg BD PO for four days, followed by 25mg mane/50mgnocte for three days followed by 50mg BD for seven days.

Intervention type

Other

Phase

Drug names

Primary outcome measures

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 two and a half hours post administration

Secondary outcome measures

1. Biological effects of exenatide is measured using blood tests at 24 hours, two and 12 weeks
2. Headaches are measured using severity scores at 24 hrs, two and 12 weeks
3. Quality of life are measured using SF-36 at baseline and 12 weeks
4. CSF exenatide levels are measured by assay at two and a half, six and 11 hours

Overall trial start date

01/06/2015

Overall trial end date

31/07/2019

Reason abandoned

Eligibility

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 type

Patient

Age group

Adult

Gender

Female

Target number of participants

Planned Sample Size: 16; UK Sample Size: 16

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

United Kingdom

Trial participating centre

Queen Elizabeth Hospital Birmingham
Mindelsohn Way Edgbaston
Birmingham
B15 2WG
United Kingdom

Trial participating centre

Sandwell General Hospital
West Midlands
West Bromwich
B71 4HJ
United Kingdom

Trial participating centre

Gloucester Royal Hospital
Great Western Road Gloucestershire
Gloucester
GL1 3NN
United Kingdom

Trial participating centre

Leicester General Hospital
Gwendolen Road
Leicester
LE5 4PW
United Kingdom

Trial participating centre

Royal Hallamshire Hospital
Glossop Road
Sheffield
S10 2JF
United Kingdom

Trial participating centre

University Hospital Coventry and Warwickshire
Clifford Bridge Road
Coventry
CV2 2DX
United Kingdom

Sponsor information

Organisation

University of Birmingham

Sponsor details

Birmingham
Birmingham
B15 2TT
United Kingdom

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Government

Funder name

Ministry of Defence

Alternative name(s)

MOD

Funding Body Type

government organisation

Funding Body Subtype

federal/national government

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Planned publication in a high impact, peer-reviewed journal, intent to publish by July 2019.

IPD sharing statement:
The current data sharing plans for the current study are unknown and will be made available at a later date.

Intention to publish date

31/07/2019

Participant level data

To be made available at a later date

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

11/08/2017: Internal review.