Thoracic low dose CT acquisition and Thoracic ultra-low dose CT acquisition

Hemorrhagic Hereditary Telangiectasia (HHT)

CT scan acquisition will be performed at 140 kVp (kilovolt peak), 10 mAs(milliampere), CTDI 1.3 mGy with an irradiation dose 0.51 mSv (milliSievert). The CT image will be reconstructed and analyzed in parenchyma window. The CT images will be blinded and re-read by two independent senior radiologists 3 to 6 weeks apart between each re-reading.

Low CT scanner without injection dose

CT acquisition will be performed at 80 kVp for patient with a body mass index<30, and 100 kVp with a body mass index>30, 10 mAs, CTDI 0.3 and 0.6 mGy with an irradiation dose 0.15-0.30 mSv. The CT images will be reconstructed and analyzed in mediastinal window. The CT images will be blinded and re-read by two independent senior radiologists 3 to 6 weeks apart between each re-reading.

Ultra-low dose CT scanner without injection

Hospices Civils de Lyon - Hopital Louis Pradel

Diagnostic Value of Ultra-low Dose Thoracic Scanner for the Pulmonary Arteriovenous Malformation Detection in HHT Patient

calculation of the sensibility, specificity and the predictive values using the Pearson's method after judgment of the presence or absence of pulmonary AVM to treat on each acquisition (low dose and ultra-low dose).

The effective dose was estimated from the product of the dose length product (DLP) using a conversion coefficient of 0.017 mSv ( milliSievert ) mGy (milligray )−1 cm−1 reported in the European Guidelines for chest examinations.

a grading score is used from "insufficient" to "good" to assess the quality of images produced by standard, iDose, and MRI reconstruction protocol

A confidence score is used (1 = no diagnostic confidence, 2 = average diagnostic confidence, 3 = good diagnostic confidence, 4 = excellent diagnostic confidence)

Hospices Civils de Lyon

Participants will receive lactose placebo tablets, encapsulated in opaque capsules, and will be asked to take one capsule daily for seven days at night-time, by mouth

Participants will receive 20mg atorvastatin tablets, encapsulated in opaque capsules, and will be asked to take one capsule daily for seven days at night-time, by mouth

Healthy

Atorvastatin 20mg

Lactose placebo

Riccardo De Giorgi

7-day Atorvastatin and Emotional Processing

The Effect of Seven-Day Atorvastatin Administration on Emotional Processing, Reward Processing, and Inflammation in Healthy Volunteers

Faces representing varying degrees [from "neutral" (0%) to "full prototypical emotion" (100%) of basic emotions (happiness, fear, anger, disgust, sadness, surprise)] are displayed on the screen and participants are asked to quickly and correctly classify them. Accuracy and reaction times on positive vs negative stimuli are compared between those receiving drug and placebo.

Faces acting as positive or negative emotional stimuli (happy or fearful facial expressions) are presented together with a matched neutral face. One is presented above and one below a central fixation point. Subsequently, a probe appears behind one of the two faces and participants are asked to quickly indicate the position of the probe. Accuracy and reaction times on positive vs negative stimuli are compared between those receiving drug and placebo.

Words describing positive and negative personality characteristics are presented, and participants are asked to quickly indicate whether they would like or dislike being described with the presented word. Accuracy and reaction times on positive vs negative stimuli are compared between those receiving drug and placebo.

After a delay from the Emotional categorisation task, participants are asked to recall and write down as many words as possible from it. Accuracy in recall of positive vs negative stimuli are compared between those receiving drug and placebo.

The original personality descriptors in the Emotional categorisation task, plus an equal number of matched distractor words, are presented, and participants are asked to indicate whether they recognise it from the Emotional categorisation task. Accuracy and reaction times on positive vs negative stimuli are compared between those receiving drug and placebo.

During a computer-based task, participants are instructed to learn and select which images are associated with wins rather than losses. Accuracy and reaction times are assessed and compared between those receiving drug and placebo.

Changes in high sensitivity-C Reactive Protein (hs-CRP) from baseline to seven-day, comparing those receiving drug and placebo

To comply with the General Data Protection Regulation (GDPR) and the new Data Protection Act, personal data will be deleted as soon as possible after it is no longer needed for the study.
Screening information: For volunteers who do not wish to be contacted for future studies, screening information (including contact details) will be stored for up to one year of completing study analyses, and then destroyed by shredding. Contact details may be retained after the end of the study for participants who have agreed to be contacted for future studies.
Consent forms: Consent forms will be kept for 10 years after the end of the study, and then destroyed by shredding.

University of Oxford

Wellcome Trust

Participants will be randomised, in a double-blind fashion, to either placebo or atorvastatin. The randomisation code will be drawn up by a researcher not involved in the study using an online randomisation tool (https://www.sealedenvelope.com/simple-randomiser/v1/lists).

The atorvastatin drug and the placebo will be encapsulated in identical capsules. Participants will not be aware of the treatment that they will be receiving; neither will the researcher. Allocation of treatments will be recorded on a Randomisation List, which will be updated when each new participant enters the randomised phase. The list will be held by a scientist uninvolved in the study.

Hereditary hemorrhagic telangiectasia patients

Hereditary Hemorrhagic Telangiectasia

5 mL dry tube to separate serum
Two 6 mL EDTA tubes for plasma separation
Eight 6 mL heparinized tubes for flow cytometry (quantification of TANG such as CD3+CD31+CXCR4+ and CEC) and quantification of angiogenesis markers.

Blood samples

Three monthly epistaxis charts to be completed

Epistaxis charts

CHU Dijon Bourgogne

Prospective Descriptive Study of the Angiogenic T Cell Population in Subjects With Hereditary Hemorrhagic Telangiectasia (HHT)

Centre Hospitalier Universitaire Dijon

Standard management for patients with spontaneous intracerebral hemorrhage according to 2015 AHA/ASA Guidelines for the Management of Intracerebral Hemorrhage
AND
Patients will have 1gram of tranexamic acid (diluted in 100ml of normal saline 0.9%) intravenously infused over 10 minutes within 3 hours of symptom presentation and another 1 gram of tranexamic acid (diluted in 100ml of normal saline 0.9%) infused over 8 hours.

Standard management for patients with spontaneous intracerebral hemorrhage according to 2015 AHA/ASA Guidelines for the Management of Intracerebral Hemorrhage
AND
Patients will 100ml of normal saline 0.9% intravenously infused over 10 minutes within 3 hours of symptom presentation and another 100ml of normal saline 0.9% infused over 8 hours.

Stroke Hemorrhagic

Intracerebral Haemorrhage

Transamine is an antifibrinolytic medication given systemically via the intravenous route

Tranexamic Acid

Kwong Wah Hospital

Tranexamic Acid for Spontaneous Acute Cerebral Hemorrhage Trial

Randomized, Double-blind, Placebo-controlled Trial to Investigate the Effectiveness of Early Intravenous Tranexamic Acid in Limiting Hematoma Expansion in Patients With Spontaneous Intracerebral Hemorrhage

Intracerebral hematoma volume (ml) as assessed by CT brain scan.

All-cause mortality within 30 days of admission

Ischemic stroke, myocardial infarction, pulmonary embolism, deep vein thrombosis

Rate of seizures within 30 days of stroke

Intolerable gastrointestinal symptoms such as dyspepsia, diarrhea, vomiting.
Allergic reaction to TXA.

Need for operative management of the hemorrhagic stroke

Peter Woo Yat Ming

Doctor

Randomised placebo-controlled parallel group clinical trial

Intravenous normal saline or transamine will be administered to subjects. Both will be of equal volume, colour and in similar intravenous fluid packaging.
The outcomes assessor will be unaware of the subject group allocation.

Haemorrhagic Hereditary Telangiectasia

Hospital Italiano de Buenos Aires

Institutional Registry of Haemorrhagic Hereditary Telangiectasia

Diego Hernan Giunta, MD

Marcelo Martin Serra

Definite clinical HHT diagnosis (at least 3 Curacao criteria) or genetic diagnosis of HHT and
Presence of Brain Arteriovenous Malformation

1. Definite clinical HHT diagnosis (at least 3 Curacao criteria) or genetic diagnosis of HHT

This is the Rare Diseases Clinical Research Networkweb site which lists the BVMC 6203 HHT study

David Geffen School of Medicine at University of California, Los Angeles

University of California, San Francisco

Yale University

Georgia Regents University

Johns Hopkins University School of Medicine

HHT Foundation International, Inc.

Mayo Clinic

Washington University School of Medicine

University of North Carolina at Chapel Hill

University of Pennsylvania School of Medicine

University of Utah

University of Alberta

St. Paul's Hospital, University of British Columbia

St. Michael's Hospital

Hospital for Sick Children

St. Antonius Hospital

Cerebral Hemorrhage Risk in Hereditary Hemorrhagic Telangiectasia

Cerebral Hemorrhage Risk in Hereditary Hemorrhagic Telangiectasia (RDCRN# 6203, Protocol Version Date 07Jan10)

This study will investigate predictors of brain outcomes in HHT patients. The investigators hypothesize that the presence of brain arteriovenous malformation (BAVM) in HHT patients versus HHT patients without BAVM and multiplicity of BAVMs will be associated with worsening functional outcome. Therefore, the comprehensive brain outcomes in HHT for future HHT clinical trials will be characterized.

The investigators hypothesize that weekly nasal bleeding duration in HHT will predict the need for invasive or life-sustaining therapies. HHT participant reported bleeding duration will be measured longitudinally and correlate with the need for invasive or life-sustaining therapies, as well as with ICH risk from BAVMs and with bleeding in other HHT organ phenotypes.

The investigators hypothesize that there are shared predictors of severe bleeding from the nose and brain in HHT patients, and that identifying these predictors will allow for selection of "at-risk" patients for clinical trials. Specifically, potential genetic, plasma protein biomarker and circulating miRNA biomarker predictors of bleeding will be evaluated. Markers associated with bleeding will then be tested for association with ICH, and with other brain outcomes and HHT severity phenotypes.