Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT05933330 |
| Other study ID # |
OP_1656 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
April 1, 2022 |
| Est. completion date |
June 30, 2025 |
Study information
| Verified date |
July 2023 |
| Source |
Odense University Hospital |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational [Patient Registry]
|
Clinical Trial Summary
With a described prevalence of brain arteriovenous malformations (CAVM) of 12.8% in HHT
patients, of whom 10% presents with intracranial hemorrhage, HHT pose a risk of devastating
intracranial hemorrhage.
The main objective of the study is to challenge current statements (pros and cons) regarding
systematic screening of asymptomatic HHT patients for neurovascular manifestations.
The investigators are thus seeking to answer a question many screening programs have faced.
A screening program should screen for a manageable problem, by a method that is considered
cost effective and does not cause negative effect, even when extrapolated to a large cohort.
Finally, the positive effect of screening program should outweigh the negative and not cause
unnecessary concerns for the patients. The investigators are seeking to draw perspectives
from the results to general questions about screening programs.
Description:
The Investigators are conducting a study investigating the disease, Hereditary Hemorrhagic
Telangiectasia (HHT) and its neuro-logical and -vascular manifestations.
With a described prevalence of brain arteriovenous malformations (CAVM) of 12.8% in HHT
patients, of whom 10% presents with intracranial hemorrhage, HHT pose a risk of devastating
intracranial hemorrhage.
The main objective of the study is to challenge current statements (pros and cons) regarding
systematic screening of asymptomatic HHT patients for neurovascular manifestations.
The investigators seek to fulfill the objective by offering all Danish HHT patients between
18-65 years of age, an MRI of the brain. Participants are asked to answer two questionnaires
(SF-36 and BDI II) before and after the MRI. 100 participants are offered an MRI ASL in
order, to investigate if this MRI sequence is more suitable to seek out vascular
malformations of the brain.
The study is being performed at the University Hospital of Odense; participants receive their
MRI at the radiological center closest to their home address. All participants are included,
informed, and briefly interviewed over the telephone. Participants will be recruited using
the Danish HHT database.
The project consist of 4 main parts.
1. Neurological manifestations of HHT.
2. A screening of all patients in the Danish HHT database, between 18-65 years of age for
CAVM.
3. A study of the adverse psychological effect from screening HHT patients in Denmark.
4. An investigation of the optimal screening method for CAVM.
Part 1
• Data included in part study 1 is collected retrospectively from the prospectively
maintained Danish HHT database.
Neurological outcomes of all patients in the database, is cross-referenced with the
Danish Apoplexy Register (DAP-database), to ensure optimal quality of registered
neurological outcomes.
Part 2
- Data included in part study 2 is MRI of brain and surgical outcome. The proposed
screening method will be conventional MRI, T1, T2 and TOF, of the cerebrum of all
HHT patients between 18-65 years of age (n=350). 100 patients will be investigated
further with MRI arterial spin labeling (ASL) and included in part 4.
Part 3 • Data included in part study 3 is SF-36 and BDI II questionaires baseline and 3
months after patients have received an MRI of the brain.
Part 4 • Data included in part study 4 is MRI of the brain, with comparative ASL
sequencing.
Separated in MRI with conventional sequences compared to MRI with ASL. Data will be
reported according to: Reporting standards for angiographic evaluation and endovascular
treatment of cerebral arteriovenous malformations, Jayaraman et al. (2011).
A cost-effectiveness analysis, investigating to prize of an MRI, the cost of additional
follow-up of vascular malformations and incidentalomas will be summarized in this part
study.
The data comes from Danish patients with HHT, 18-65 years of age. Continues data is
expected to have normal distribution, and will be tested by the shapiro-wilk test.
In case of normal distribution, oneway anova will be used to test significant levels of
difference between the 5 groups (HHT1, HHT2, JP-HHT, Unknown HHT status and not
genetically verified).
If data is not normally distributed Kruskal-Wallis test will be used to test
significance.
Multivariate analyses will be done by logistic regression and in case of non-binary
ordered data, ordered logistic regression adjusting for age and gender will be used.
Dichotomous categorical data will be analyzed of their degree of independence with chi2
test.
As HHT is inherited autosomal dominantly, and The sample group is only selected by age
(18-65 years of age), The investigators expect data to have normal distribution. In case
of lack of normal distribution, this could be explained by the fact that HHT is a rare
disease with varying penetrance.
A power analyses for the project shows:
For the BDI II and SF-36 outcomes with 289 patients a mean change from pre-screening to
post-screening could be detected with 80% power if:
- Pre-post-correlation = 0.5 (assumed to be the lowest realistic value): Change of
0,17 SD could be detected
- Pre-post-correlation = 0.8 (assumed to be the highest realistic value): Change of
0,10 SD could be detected As a clinical relevant difference typically would be
assumed to be at least 0,3 SD, any clinical relevant changes should be detectable
with 289 patients.
A preliminary investigation indicates a 95% inclusion rate (5% of patients does not want
to participate, or has already recieved an MRI of brain prior to the study). The
investigators expect patients to be less likely to answer the questionnaire send to them
3 months after they have received the results from their brain MRI. Every Friday after
initial invitation to the follow-up questionnaire, a reminder will be sent to the
patients. after 3 reminders, the patients will finally be called.
Part 4 - optimal MRI ASL (arterial spin labeling). In order for this study to be
successful, The study need at least 10 patients whom have received a brain MRI with ASL
that found a Cerebral AVM. In case of lacking case patients, HHT patients who have
received an ordinary MRI with angio-sequences, that showed a cerebral AVM will be
invited to have an brain MRI with ASL. This examination is done to uncover whether the
participants have more cerebral AVM, that is not visible on conventional MRI. previous
studies has shown, that roughly, 50% of HHT patients with cerebral AVM has multiple
AVMs.
The Danish HHT center has been situated at Odense University Hospital since 1996 and all
HHT patients seen at the center have been included in the national research ´database.
In 2015 data were uploaded in a Red Cap database and since then all patients included in
the database have received written information and given informed consent. Data
regarding date of birth, age, age of diagnosis, HHT type, results of screening for PAVM,
CAVM and hepatic AVM (HAVM) are included. Furthermore, data regarding age of debut of
epistaxis, results regarding date of neurological events, cerebral ischemia, bleeding,
and abscess are also included in the Danish HHT database.
The study and its part studies, contains personal patient data, and is therefore under
the GDPR act.
The project is approved by the Danish Data Protection Agency and the Region of Southern
Denmark´s regional secretariat of Law.
Data from this project is owned by the Danish HHT-center, and is located at the
department of ear, nose and throat surgery at OUH.
ALL data is only published in anonymized form. Data is only exported from RedCap in
pseudononymized form for the purpose of statistical analyses.
