Objectivesi)) To study whether reproductive hormones play a role in migraine susceptibility in malemigraine patients; ii) to study functionality of the trigeminal system prospectively duringinterictal and premonitory phases of the migraine attack (…
ID
Source
Brief title
Condition
- Endocrine disorders of gonadal function
- Headaches
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Outcome measures
For the levels of reproductive hormones, we will focus on intra-individual
variability in
testosterone : oestradiol ratio (T/E) in migraineurs during different phases of
the migraine
attack, with the log[T/E] as primary outcome additionally, we will compare this
intraindividual
variability in migraineurs with those in controls. For salivary measurements, we
will focus on amount of peptides (milligrams) produced per time period and
compare
migraineurs with controls, and between different migraine phases. In blink
reflex testing, we
will compare blink reflex latencies, duration, amplitudes and area under the
curve (AUC)
between migraineurs and controls, and between different migraine attack phases.
Secondary outcome
not applicable
Background summary
Introduction
Migraine susceptibility is modulated by reproductive hormones and
neuropeptides. Women
suffer from migraine far more frequently than men and the migraine attack
frequency is
related to both different phases of the menstrual cycle and different
reproductive phases in
female life. Female reproductive hormones can also be detected in males, albeit
in lower
levels. Whether these hormones play a role in migraine susceptibility in males
is unclear. In
migraine pathophysiology, trigeminal activation plays a key role. Neuropeptides
such as
CGRP have been shown to trigger migraine and CGRP levels are increased during
the
headache phase of a migraine attack, reflecting abnormal activation of the
trigeminal
system. Whether the trigeminal system is already in a different state during
the prodromal
phase of an attack, is not known yet.
Study objective
Objectives
i)) To study whether reproductive hormones play a role in migraine
susceptibility in male
migraine patients; ii) to study functionality of the trigeminal system
prospectively during
interictal and premonitory phases of the migraine attack (salivary CGRP and
blink reflex);
iii) To correlate this trigeminal sensitivity during interictal and premonitory
phases to
circulating levels of reproductive hormones;
Study design
Methods
Male migraineurs (n=20) and male controls (n=20) will be included. Serum
sampling will be
performed 1) in controls (n=20) on one day at 4 different time points; ii) in
migraineurs
(n=20) in at maximum 10 consecutive days (including interictal and premonitory)
at 4
different time points per day. Levels of reproductive hormones (testosterone,
oestradiol and
SHBG) will be measured. Blink reflex measurements will be performed 1) in
controls (n=20)
on one day at 4 different time points; ii) in migraineurs (n=20) in at maximum
10
consecutive days (including interictal and premonitory) at 4 different time
points per day.
Blink reflexes will be assessed to test responsiveness and functionality of the
trigeminal
system. Salivary sampling will be performed in a subgroup of migraineurs (n=10)
in at
maximum 10 consecutive days (including interictal and premonitory) at 5
different time
points per day, after which salivary levels of neuropeptides CGRP and VIP will
be
assessed. A capsaicin provocation model will be used to assess sensitivity of
the trigeminal
system. Between-groups and within-subject comparisons will be performed for
different
conditions using appropriate statistics.
Study burden and risks
Migraine pathophysiology is not completely understood, especially when it comes
to the phase preceding the actual headache phase. We assume severeal biological
systems may change over time during the approach of an upcoming migraine
attack. In this study, we use a multimodal approach to assess functionality of
several differents systems/ mechanisms, that are likely to be involved in the
onset of the migraine headache. Until now, synchronic measurements on these
most-promising systems (gonadal hormones; brainstem trigeminal sensitivity and
peripheral trigeminal sensitisation) has not been performed. Results from this
study might help identify pathways or mechanisms that trigger the onset of
migraine attacks, and might therefore be helpfull in developping prophylactic
anti-migraine medication.
We think the burden to participants is balanced to the richness of the data
that will result from this study.
Albinusdreef 2
2333 ZA Leiden
NL
Albinusdreef 2
2333 ZA Leiden
NL
Listed location countries
Age
Inclusion criteria
Migraine patients
Inclusion criteria are: i) males; ii) migraine with/ without aura according to the IHS criteria;
ii) baseline attack frequency of 1 to 3 attacks per month; iii) moderate or severe headache
during attacks; iv) age >18 years.;Healthy controls
Healthy volunteers will be age and gender matched.
Exclusion criteria
Migraineurs:
Exclusion criteria are: i) more than 10 days of headache
per month; ii) inability to differentiate between migraine and other forms of headache; iii)
suffering from only migraine auras/ migraine sans migraine; iv) current use of medication
influencing reproductive hormone levels; v) use of prophylactic anti-migraine medication; vi)
Body Mass Index (BMI) under 20 or above 28; or vii) current smoking (nicotine is known to
increase CGRP release96); viii) frequent consumption of spicy foods; ix) severe arterial
hypertension97; x) intake of high-fat foods directly before measurements (as is suggested to
influence plasma CGRP levels98;99).;Healthy controls
Exclusion criteria are i) personal or
first-degree-relative history of migraine or other primary headache syndrome, except
infrequent episodic tension type headache; ii) headache on >2 days per month; iii) BMI <20
or >28; iv) current use of medication influencing reproductive hormone levels; v) current
smoking96; vi) severe arterial hypertension97; vii) intake of high-fat foods directly before
measurements (as is suggested to influence plasma CGRP levels98;99); viii) frequent consumption of spicy foods
Design
Recruitment
metc-ldd@lumc.nl
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL36376.058.11 |