An observational study in Cluster Headache, sponsored by IRCCS National Neurological Institute "C. Mondino" Foundation. Recruiting at 1 site in Italy. Open to participants aged 18 Years to 65 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2024-07-16.
Sponsored by IRCCS National Neurological Institute "C. Mondino" Foundation · Observational
Among 14 studies in Cluster Headache with a site in Italy — 4 open to participants now, 4 under way, 1 of them phase 3. Cluster Headache · Italy.
Among the 14 studies in Cluster Headache with a site in Italy, this one is the only one that started in 2023, is one of 3 observational ones, and was the 13th registered.
123 studies on the registry are indexed under Cluster Headache; 26 are open to participants now.
This study's planned enrollment of 100 is above the median of 68 across 32 observational studies indexed under Cluster Headache.
Browse Cluster Headache studies →4 of the 14 studies in Cluster Headache with a site in Italy are open now, in 5 countries. Each count lists the studies.
Of the 18 Cluster Headache studies recruiting now, 7 (39%) set no upper age limit and 6 (33%) stop at 75 or younger; 4 take children under 18; 4 take healthy volunteers.
This study: 18 Years to 65 Years · all sexes · healthy volunteers too.
The full table on the hub →14 studies; the count open now beside each. This study's row is marked.
First in 2012; this study’s year is marked. 1 started in 2023.
Median enrollment 165 across the 11 interventional studies, 100 across the 3 observational. Of the 10 that completed or were terminated, 9 (90%) have results posted.
9 of 14 have an industry lead sponsor. The 8 most frequent:
IRCCS National Neurological Institute "C. Mondino" Foundation is the lead sponsor of 57 studies on the registry; 20 are open to participants now.
IRCCS National Neurological Institute "C. Mondino" Foundation has 2 studies filed under Cluster Headache — fewer than ten, so there is no comparison to draw.
None of the studies under way reaches primary completion within a year.
Among the 14 studies in Cluster Headache with a site in Italy, from their registry updates:
Nothing recorded among them since 2026-09-25.
Cluster headache (CH) is a primary headache included in the trigeminal autonomic cephalalgias (TACs) according to the International Calssification of Headache Disorder, Third Edition. CH is characterized by a multifaceted and incompletely understood pathophysiology. Recent experimental evidence has increasingly emphasized the role of specific microRNAs (miRNAs) in the pathophysiology of primary headaches, including migraine.
In a recent study, we observed an upregulation in the gene expression of two miRNAs, miR-382-5p and miR-34a-5p, in peripheral blood mononuclear cells (PBMCs) of subjects with chronic migraine (CM). These miRNAs are involved in inflammation modulation and the release of γ-aminobutyric acid (GABA). Notably, this upregulation correlated with the migraine phenotype and its severity.
Several neuropeptides have been established to play an active role in CH. Studies by the Danish group have demonstrated that intravenous administration of CGRP, PACAP, or VIP can induce CH attacks in at least 50% of participants in the active phase of the disease.
However, no data currently exists regarding the potential involvement of miRNAs in CH. Given this context, the primary aim of this study is to investigate the gene expression of specific miRNAs (miR-382-5p, miR-34a-5p, and miR-155) in PBMCs and plasma levels of neuropeptides (CGRP, PACAP, VIP) in subjects with episodic CH in the active phase (eCH-act), episodic CH in the remission phase (eCH-rem), chronic CH (cCH), and healthy control subjects (HCs).
Background Cluster headache (CH) is a primary headache included in the trigeminal autonomic cephalalgias (TACs) according to the International Calssification of Headache Disorder, Third Edition. CH is characterized by a multifaceted and incompletely understood pathophysiology. The hypothalamus, the trigeminal-vascular complex, and the trigeminal-autonomic reflex are believed to play a significant role.
Increasing experimental evidence has highlighted the involvement of specific microRNAs (miRNAs) in the chronic pain and primary headaches, including migraine. miRNAs are small endogenous noncoding RNAs that are around 22 nucleotides in length. miRNAs operate as post-transcriptional regulator of gene expression by promoting messenger RNA (mRNA) degradation or repressing mRNA translation. The regulation process performed by miRNAs is complex and articulated since an individual miRNA might target hundreds of different mRNAs, and conversely, each mRNA may be regulated by multiple miRNAs. It has been estimated that more than 60% of all protein-coding genes are regulated by miRNAs which consequentially determine the pleiotropic modulation of a wide variety of cellular processes involving differentiation, development and signaling. miRNAs are involved in the generation and maintenance of pain and several evidence suggest that specific miRNAs could play a role in migraine.
In a recent study, we observed an upregulation of gene expression in two miRNAs, miR-382-5p and miR-34a-5p, in peripheral blood mononuclear cells (PBMCs) in subjects with chronic migraine (CM). These miRNAs are involved in inflammation modulation and the release of γ-aminobutyric acid (GABA) compared to individuals with episodic migraine and healthy subjects (HCs). These findings underscore a correlation between the gene expression of these miRNAs and the migraine phenotype, as well as its severity.
Recent studies suggest an active role for certain neuropeptides in CH. The Danish group has indeed demonstrated that the intravenous administration of CGRP, PACAP, or VIP can induce acute CH attacks in at least 50% of participants when studied in the active phase of the disease.
As of now, there is no data regarding the potential involvement of miRNAs in CH. This study aims to provide a detailed exploration of the role of miRNAs in cluster headache, contributing to our understanding of the pathophysiology of this primary headache disorder. Furthermore, the results obtained may pave the way for the development of a new generation of molecules that could be used in the field of CH, such as miRNA agonists (Agomir) and antagonists (Antagomir).
Aims The primary objective of our current project is to investigate the peripheral expression of miRNAs implicated in pain modulation (miR-382-5p, miR-34a-5p, and miR-155) in subjects with episodic CH in the active phase (eCH-act), episodic CH in the remission phase (eCH-rem), chronic CH (cCH), and healthy control subjects (HC).
Methods
All subjects will perform a single evaluation over time during which they will undergo:
All subjects will be evaluated in the morning, after night fasting. For subjects affected by cCH or eCH-act, sampling is expected to be carried out in the inter-critical phase, as defined by the absence of CH attacks for at least 3 hours in patients with eCH and for at least 8 hours in patients with cCH. After blood sampling, patients will stay at Center to complete a set of questionnaires. This will allow the investigator to monitor the patients for at least 2 hours, to exclude that a blood sampling is performed immediately before a CH attack.
For patients with eCH, the "active" and "remission" phases will be defined as follows:
miR-382-5p, miR-34a-5p and miRNA-155 gene expression will be evaluated in PBMCs by real-time reverse transcription (RT-PCR). This assessment will be normalized with U6 (a type of small nuclear RNA used as housekeeping gene) and expressed as Relative Quantification (RQ). Plasma levels of CGRP alpha, PACAP and VIP will be measured using validated commercial ELISA kits. A detailed description of the methods planned for the biochemical analyses could be found here: https://doi.org/10.1186/s10194-020-01189-0.
The set of clinical questionnaires will include: Migraine Disability Assessment (MIDAS), Headache Impact Test (HIT-6), Cluster headache Impact Questionnarie (CHIQ).
Sample size calculation and pre-planned statistical analysis The following parameters were considered for the calculation: Effect Size: 0.5; alpha error: 0.05; beta error: 0.05 (power: 95%); number of groups: 4.
Sample size calculation was conducted using the freeware platform G*Power (ver. 3.1.9.7) for an ANOVA test with Bonferroni correction applied to the 4 groups. The minimum suggested sample size is 76 subjects (19 subjects per group). To account for potential variability, we plan to enroll a total of 100 subjects, with 25 subjects per group.
Parametric or non-parametric correlations will be used to measure the relationship between biochemical variables and clinical variables. Multivariate analyses will be performed according to the results of the univariate analysis. Statistical significance will be set at the 5% level (p\<0.05).
We aim to enroll a representative population of patients affected by eCH in the active phase and in the remission phases and cCH. All patients will be consecutively enrolled among those attending the clinics of the Headache Science Center of the IRCCS Mondino Foundation of Pavia (Italy).
A set of healthy controls, without a present or past diagnosis primary or secondary headaches, will be enrolled as control group.
Inclusion Criteria:
Exclusion Criteria:
Inclusion Criteria:
Exclusion Criteria:
Inclusion Criteria:
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Healthy subjects without present or past history of headache according to ICHD-III criteria.
Patients with a diagnosis of "3.1.1 Episodic Cluster Headache", according to ICHD-III criteria.
Patients with a diagnosis of "3.1.2 Chronic Cluster Headache", according to ICHD-III criteria.
PBMCs gene expression of miR-382-5p
miR-382-5p gene expression in PBMCs will be evaluated by real-time reverse transcription (RT-PCR). This assessment will be then normalized with U6 (a type of small nuclear RNA used as housekeeping gene) and expressed as Relative Quantification (RQ).
Time frame: Single evaluation at study visit - baseline (T0)
PBMCs gene expression of miR-34a-5p and miR-155
miR-34a-5p and miRNA-155 gene expression will be evaluated by real-time reverse transcription (RT-PCR). This assessment will be then normalized with U6 (a type of small nuclear RNA used as housekeeping gene) and expressed as Relative Quantification (RQ).
Time frame: Single evaluation at study visit - baseline (T0)
Plasma levels of CGRP alpha, PACAP and VIP
Plasma levels of CGRP alpha, CGRP beta, PACAP and VIP will be measured using validated commercial ELISA kits.
Time frame: Single evaluation at study visit - baseline (T0)
Score of MIDAS, HIT-6, and CHIQ
MIDAS, HIT-6, CHIQ represent validated clinical scales to rate CH related disability.
Time frame: Single evaluation at study visit - baseline (T0)
Started Mar 2023 (actual). Primary completion is estimated for Dec 2024, 21 months after the start.
How these figures are worked out, and which studies are left out of them.
Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.
Contact study teamGet an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
IRCCS National Neurological Institute "C. Mondino" Foundation