Condition category
Nervous System Diseases
Date applied
25/09/2008
Date assigned
07/10/2008
Last edited
11/01/2012
Prospective/Retrospective
Prospectively registered
Overall trial status
Stopped
Recruitment status
Stopped

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr William Whitehouse

ORCID ID

Contact details

University of Nottingham
E Floor East Block
Queen’s Medical Centre
Nottingham
NG7 2UH
United Kingdom
+44 (0)115 924 9924 ext 63328
william.whitehouse@nottingham.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

HTA 05/15/01; 29372

Study information

Scientific title

A double-blind parallel-group randomised placebo-controlled trial of propranolol and pizotifen in preventing migraine in children

Acronym

P3MC

Study hypothesis

1. Propranolol is superior to placebo for the prevention of migraine attacks in children aged 5 - 16 years
2. Pizotifen is superior to placebo for the prevention of migraine attacks in children aged 5 - 16 years

More details can be found at http://www.hta.ac.uk/1526
Protocol can be found at http://www.hta.ac.uk/protocols/200500150001.pdf

Ethics approval

Trent Research Ethics Committee (REC) approved in November 2008 (ref: 09/H0405/19)

Study design

Parallel-group randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Other

Trial type

Treatment

Patient information sheet

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

Condition

Paediatric migraine

Intervention

Eligible participants will be randomly allocated to the following four arms after the 4-week run-in period, double blind:

Arm 1 (n = 200): Propranolol (oral; tablet or liquid):
Children aged 5 - 7:
Week 1: 10 mg twice daily (bd)
Week 2: 20 mg bd
Week 3 - 14: 30 mg bd

Children aged 8 - 11:
Week 1: 20 mg bd
Week 2: 30 mg bd
Week 3 - 14: 40 mg bd

Children aged 12 - 16:
Week 1: 30 mg bd
Week 2: 40 mg bd
Week 3 - 14: 60 mg bd

Week 15 - 16: Dose of the drug will be reduced gradually before stopping completely

Arm 2 (n = 200): Pizotifen (oral; tablet or liquid):
Children aged 5 - 7:
Week 1: placebo + pizotifen 500 µg once daily (od)
Week 2: placebo + pizotifen 1 mg od
Week 3 - 14: placebo + pizotifen 1.5 mg od

Children aged 8 - 11:
Week 1: placebo + pizotifen 1 mg od
Week 2: placebo + pizotifen 1.5 mg od
Week 3 - 14: placebo + pizotifen 2 mg od

Children aged 12 - 16:
Week 1: placebo + pizotifen 1.5 mg od
Week 2: placebo + pizotifen 2 mg od
Week 3 - 14: placebo + pizotifen 3 mg od

Week 15 - 16: Dose of the drug will be reduced gradually before stopping completely

Arm 3 (n = 100): Propranolol placebo control group

Arm 4 (n = 100): Pizotifen placebo control group

Amended as of 11/01/2012, the trial was stopped early due to poor recruitment at the end of June 2011.

Intervention type

Drug

Phase

Not Specified

Drug names

Propranolol, pizotifen

Primary outcome measures

Number of migraine attacks during weeks 11 to 14

Secondary outcome measures

1. Response defined as a 50% or greater reduction in number of attacks. Duration of follow-up: 42 weeks.
2. Headache intensity (headache diary). Duration of follow-up: 14 weeks.
3. Use of rescue medication. Duration of follow-up: 14 weeks.
4. School attendance. Duration of follow-up: 14 weeks.
5. Parent/guardian time off work during weeks 11 to 14
6. Recalled attack frequency. Duration of follow-up: 14 weeks.
7. Quality of life and functional outcomes: Paediatric Migraine Disability Assessment (PedMIDAS), Generic Child Quality of Life measure (GCQ), parent Euroqol EQ-5D, child Euroqol EQ-5D

Overall trial start date

01/06/2009

Overall trial end date

01/07/2012

Reason abandoned

"Participant recruitment issue"

Eligibility

Participant inclusion criteria

1. Both males and females, age 5 years 0 months to 16 years 11 months
2. With Migraine with Out aura (MO), Migraine with Aura (MA), Probable Migraine (PM) as defined by the International Headache Society (IHS1) criteria, with 2 to 6 migraine or probable migraine attacks/ 4 weeks by history during the previous 3 months
3. Two to 6 migraine or probable migraine attacks/ 4 weeks during the 4 week run-in
4. Treating paediatrician and parent/ guardian and child or young person believe the attacks are currently frequent and severe enough to merit a try of twice daily preventative medication
5. Satisfactory completion of headache diary during the run-in period at discretion of the investigator

Participant type

Patient

Age group

Child

Gender

Not Specified

Target number of participants

600 (Poor recruitment, study stopped at the end of June 2011)

Participant exclusion criteria

Amended as of 13/07/2009:
1. Asthma, bronchospasm or nocturnal or exercise induced cough or wheeze within the last 12 months or currently on daily asthma preventative treatment
2. Children under paediatric cardiology review, at the discretion of their paediatric cardiologist, e.g. if propranolol or pizotifen were contraindicated
3. Children with any of the following: uncontrolled heart disease, the presence of second or third degree heart block, in cardiogenic shock, bradycardia, severe peripheral arterial disease, metabolic acidosis, sick sinu syndrome, untreated phaeochromocytoma, prone to hypoglycaemia (e.g. after prolonged fasting) or Prinzmetal's angina
4. Previous severe adverse event probably related to propranolol or pizotifen
5. On propranolol, another beta-blocker, pizotifen or cyproheptidine in the last 3 months
6. Currently in or have been in another prospective drug trial in the last 3 months
7. Fewer than two or more than six eligible attacks during the 4 week run-in, and stay excluded for 3 months at least
8. Child or family unable to identify their migraine or probable migraine headaches confidently (as may happen with some patients with both mild headaches and migraine on different days, e.g. with chronic daily headache [15 or more headache days/month])
9. Females of child bearing potential who are not using a reliable contraceptive strategy such as abstinence, barrier methods, oral contraceptive pills and contraceptive injections
10. Informed consent not given by parents/guardian, or assent/consent not given by patient

Initial information at time of registration:
1. Asthma or nocturnal or exercise induced cough or wheeze within the last 12 months or currently on daily asthma preventative treatment
2. Children under paediatric cardiology review, at the discretion of their paediatric cardiologist, e.g., if propranolol or pizotifen were contraindicated
3. Previous severe adverse event probably related to propranolol or pizotifen
4. On propranolol, another beta-blocker, pizotifen or cyproheptidine in the last 3 months
5. Currently in or have been in another prospective drug trial in the last 3 months
6. Fewer than 2 or more than 6 eligible attacks during the 4 week run-in, and stay excluded for 3 months at least
7. Child or family unable to identify their migraine or probable migraine headaches confidently (as may happen with some patients with both mild headaches and migraine on different days, e.g., with chronic daily headache [15 or more headache days/month])
8. Females of child bearing potential who are not using a reliable contraceptive strategy such as abstinence, barrier methods, oral contraceptive pills and contraceptive injections
9. Informed consent not given by parents/guardian, or assent/consent not given by patient

Recruitment start date

01/06/2009

Recruitment end date

01/07/2012

Locations

Countries of recruitment

United Kingdom

Trial participating centre

University of Nottingham
Nottingham
NG7 2UH
United Kingdom

Sponsor information

Organisation

University of Nottingham (UK)

Sponsor details

Research Innovation Services
King's Meadow Campus
Lenton Lane
Nottingham
NG7 2NR
United Kingdom

Sponsor type

University/education

Website

http://www.nottingham.ac.uk

Funders

Funder type

Government

Funder name

NIHR Health Technology Assessment Programme - HTA (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

1. 2010 protocol in http://www.ncbi.nlm.nih.gov/pubmed/20553601

Publication citations

  1. Protocol

    Silcocks P, Whitham D, Whitehouse WP, P3MC: a double blind parallel group randomised placebo controlled trial of Propranolol and Pizotifen in preventing migraine in children., Trials, 2010, 11, 71, doi: 10.1186/1745-6215-11-71.

Additional files

Editorial Notes