Condition category
Signs and Symptoms
Date applied
07/02/2019
Date assigned
08/02/2019
Last edited
12/02/2019
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Cough headache is a very rare headache type that accounts for less than 1% of the diagnoses in specialised headache centres. By targeting a population from a cough clinic, this study aims to provide a better evidence on what the headache characteristics and other associated features are.

Who can participate?
Patients aged 18-80 with cough headache

What does the study involve?
The study consists of one visit. Participants go through a semi-structured interview in which general medical history and features of headache are assessed. A neurological examination is performed as well as modified Valsalva Test.

What are the possible benefits and risks of participating?
If the study were to find a likely diagnosis of cough headache, specific and more directed treatment could be recommended to the patient’s GP if this has not been the case to date. The modified Valsalva test may cause or worsen headache for a brief period of time. Potentially, if performed in cough headache patients it could cause a similar headache to the one they would get when they cough, and it would presumably resolve within minutes. There are no other known risks of participating on this trial.

Where is the study run from?
King’s College Hospital (UK)

When is the study starting and how long is it expected to run for?
February 2019 to February 2020

Who is funding the study?
National Institute for Health Research (NIHR) (UK)

Who is the main contact?
Dr David Moreno Ajona
david.1.moreno_ajona@kcl.ac.uk

Trial website

Contact information

Type

Public

Primary contact

Dr David Moreno Ajona

ORCID ID

http://orcid.org/0000-0002-0366-5994

Contact details

Denmark Hill
London
SE5 9RS
United Kingdom
+44 (0)2032995525
david.1.moreno_ajona@kcl.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

KCH19-021

Study information

Scientific title

Description of primary cough headache in a cough unit: a prospective study

Acronym

PCH-CU

Study hypothesis

According to the current available data, primary cough headache (PCH) occurs mainly in subjects over the age of 40 years, being the mean age of onset 67 years. A male predominance has been pointed, although the male/female ratio changes dramatically among series. Furthermore, it seems to be an episodic disease as it normally lasts less than 2 years. Pain is usually localized bilaterally, with a major involvement of the occipital region. Pain quality, however, has been described as sharp, stabbing, splitting, explosive, electrical, pressing, dull or even pulsatile. Precipitants may include coughing, sneezing, nose blowing, laughing, crying, singing, lifting a weight, straining at stool, and stooping. Nevertheless, they should not include sustained physical exercise which would be typical of exertional headache. Regarding the headache associated features, nausea, dizziness and photo/photophobia have been documented in a very little proportion of patients, being these, vertigo, ataxia and syncope, red flags indicating a probable secondary origin.

In this context, differential diagnosis with secondary or symptomatic cough headache is crucial. The most common reported cause is Chiari type 1 malformation, although any posterior fossa lesion could cause the symptoms as well as syringomyelia, platybasia, obstructive hydrocephalus, subdural hematoma, sphenoid sinusitis, spontaneous intracranial hypotension, brain aneurysm and even carotid artery disease. Overall, it is considered that almost 50% of cough headaches are symptomatic. However, the only published study in cough patients found 3/32 (9%) secondary headaches (all of them due to Arnold Chiari malformation).

A 16-patient study showed that a modified Valsalva manoeuvre (exhalation into the spigot of an aneroid sphygmomanometer to a pressure of 60 mm Hg and maintain this for 10 seconds) was capable of distinguishing primary from secondary headache. According to this result, the authors hypothesized that a transient increase in intracranial pressure during exertion due to obstruction to normal CSF dynamics should explain secondary Cough headache. Conversely, they stated PCH could be caused through congestion of the orbital venous plexus in the presence of jugular venous incompetence and a reduced threshold for trigeminal sensory activation. On the other hand, it is argued that a relative obstruction of CSF flow could take place, following research by Chen et al., who described a more crowded posterior fossa in PCH patients.

PCH may respond to Indomethacin (50-150 mg daily) which has also been attributed to its carbonic anhydrase inhibitor property, leading to decreased intracranial pressure.

Knowledge on the clinical aspects of this disorder is a necessary step towards the understanding of the pathophysiology and subsequent development of targeted therapies, hence, a better description of PCH patients is required.

Ethics approval

South East Scotland Research Ethics Committee 01, Waverley Gate, 2-4 Waterloo Place, Edinburgh, EH1 3EG, Tel: +44 (0)131 465 5473, Email: Sandra.Wyllie@nhslothian.scot.nhs.uk, 30/01/2019, REC ref: 18/SS/0165, Protocol number: 1, IRAS project ID: 256341

Study design

Cross-sectional cohort study

Primary study design

Observational

Secondary study design

Cross sectional study

Trial setting

Hospitals

Trial type

Diagnostic

Patient information sheet

Not available in web format, please use contact details to request a participation information sheet.

Condition

Primary cough headache

Intervention

The study consists of one visit. Previously, a pre-screening questionnaire performed at the cough clinic will determine potential eligibility. Study visit: consent will be sought and, after screening, eligible participants will go through a semi-structured interview in which general medical history and features of headache will be assessed. Neurological examination will be performed as well as a modified Valsalva Test.

Intervention type

Other

Phase

Drug names

Primary outcome measure

The clinical features and prevalence of cough headache in patients attending a Cough Unit and the differences between primary and secondary cough headache, measured using questionnaire adapted from the usual headache clinic and cough clinic interviews at the single study visit.

Secondary outcome measures

Measured using questionnaire adapted from the usual headache clinic and cough clinic interviews at the single study visit:
1. Specific comorbidities related to cough headache
2. The use of opioids and other drugs in cough patients and possible relationship with the development of chronic headache
3. The utility of the modified Valsalva manoeuvre in these patients

Overall trial start date

06/02/2019

Overall trial end date

06/02/2020

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Patients are capable of giving signed informed consent indicating that the subject has been informed of all pertinent aspects of the trial detailed in the patient information sheet (PIS), informed consent form (ICF), and in the protocol
2. Subjects must be willing to receive a telephone call or travel to and from King’s College Hospital as preferred, during normal working hours
3. Diagnosis of Primary Cough Headache (PCH) using criteria previously published
4. Aged 18-80 years inclusive
5. Willing and able to comply with scheduled visits and study procedures

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

50

Participant exclusion criteria

1. Pregnancy or breastfeeding from consent until the end of study involvement
2. History of psychosis, depression or psychological diseases either (a) requiring ongoing psychoactive drugs, or (b) that the Investigator has reason to believe will either affect the patient’s neural pathways or hinder the performance of the patient with regard to ability to successfully complete the tasks required of them according to the protocol
3. History/presence of cerebral haemorrhage, brain tumour, brain aneurysm, cryptococosis or other brain mass lesion within the last 12 months
4. Any other medical condition that in the opinion of the Investigator would make the subject unsuitable for the study
5. Inclusion to another research study within the past 30 days

Recruitment start date

11/02/2019

Recruitment end date

20/10/2019

Locations

Countries of recruitment

United Kingdom

Trial participating centre

King's College Hospital
Denmark Hill
London
SE5 9RS
United Kingdom

Sponsor information

Organisation

King's College London

Sponsor details

Denmark Hill
London
SE5 9RS
United Kingdom
+44 (0)2032991981
reza.razavi@kcl.ac.uk

Sponsor type

University/education

Website

https://www.kcl.ac.uk/index.aspx

Organisation

King’s College Hospital NHS Foundation Trust

Sponsor details

Denmark Hill
London
SE5 9RS
United Kingdom
+44 (0)2032991981
reza.razavi@kcl.ac.uk

Sponsor type

Hospital/treatment centre

Website

https://www.kch.nhs.uk/

Funders

Funder type

Government

Funder name

NIHR BRC grant – Pain theme

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

The results of this study will be published in acclaimed international journals, relevant to the field of study.

IPD sharing statement
Each patient will be assigned a study number. Personal Identifiable Information (PII) and medical records from participants recruited at the site (King’s College Hospital) will be de-identified and recorded on source documents created specifically for the study. Source documents from participants recruited at the site (King’s College Hospital) and consent forms will be stored in the Headache Group, Clinical Research Office, Welcome Foundation Building, Denmark Hill Campus, King’s College London. Access to this office is restricted and paperwork is stored in locked filing cabinets.
Source documentation collected will be stored as per local data protection standard operating procedures.
Clinical data from source documents will be entered by an investigator into an Excel database in an anonymized format, locked with a password and kept on a KCH computer. PII will be kept on a different Excel file on a different KCH computer, also locked with a different password than the other file. KCH computers are located in the same office which is locked and accessible to the investigators only.
King’s College Hospital will keep identifiable information about participants for 12 months after the study has finished.
During study conduct, data will be reviewed to ensure that the protocol and Good Clinical Practices are being followed. Source document may be reviewed to confirm that data recorded on the CTF is accurate. The site may be subject to review by the Independent Ethics Committee and/or to inspection by appropriate regulatory authorities. The investigator and relevant personnel will ensure that they will be available during monitoring and possible audits and inspections.
No identifiable information will be provided. For any other documents, please contact the Institute of Psychiatry, Psychology and Neuroscience (King’s College London), Headache Group on:
Dr David Moreno
Clinical Research Fellow
King’s College London
London SE5 9PJ
Tel: 020 3299 5525
Email: david.1.moreno_ajona@kcl.ac.uk

Intention to publish date

06/02/2021

Participant level data

Available on request

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

12/02/2019: Uploaded protocol Version 2.2, 28 January 2019 (not peer reviewed).