RecruitingPhase IIInterventional

An evaluation of two drugs for treating a familial form of pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is a serious condition causing high blood pressure in the blood vessels supplying the lungs. While current treatments manage symptoms, they do not fix the root cause. In some people, the condition is linked to an inherited change in a gene called BMPR2. This clinical trial, called StratosPHere 2, is testing two medicines: hydroxychloroquine and glycerol phenylbutyrate. Both drugs are already used safely in the UK for other medical conditions. Scientists believe they might help correct how the BMPR2 gene works in the lungs. Participants will carry on with their normal PAH care and will be chosen by chance to take either one of the trial drugs or a dummy treatment (placebo). Doctors will closely check their health through blood tests and heart tracings to see if these drugs offer a safe, new way to tackle the underlying cause of PAH.

At a glance

Status

Recruiting

Phase

Phase II

Sponsor

Papworth Hospital NHS Foundation Trust

Enrolment target

Start

11 Dec 2023

Estimated completion

01 Dec 2026

Pulmonary arterial hypertension

What is this study about?

Pulmonary arterial hypertension, often called PAH, is a condition where the blood vessels leading to the lungs become stiff, narrow, or thick. This makes it harder for blood to flow through, which raises blood pressure in the lungs and puts extra strain on the right side of the heart. Over time, this can cause breathlessness, fatigue, and dizziness. Existing NHS treatments are good at relaxing these blood vessels to ease symptoms, but they cannot cure the condition or repair the underlying damage.

In some families, PAH is linked to an alteration in a gene called BMPR2. Genes are the instruction manuals inside our cells, and BMPR2 helps keep the blood vessels in the lungs healthy. When this gene does not work properly, the blood vessels are more likely to become damaged and narrow. Until now, doctors have not had any treatments that directly target how this gene behaves.

Researchers at the Royal Papworth Hospital NHS Foundation Trust are leading a study to see if they can change that. Instead of inventing entirely new drugs from scratch, they are testing two medicines that are already used for other illnesses: hydroxychloroquine (often used for arthritis) and glycerol phenylbutyrate (used for metabolic conditions). Laboratory tests show that both medicines may help the body process the BMPR2 gene better.

By comparing these medicines against a dummy treatment (placebo) alongside normal PAH care, the study team hopes to learn whether repurposing existing medicines can tackle the true cause of this condition. If successful, this research could lead to more targeted, effective treatments for people living with inherited PAH.

Key takeaways

Tests two existing UK-approved medicines to treat the root cause of inherited PAH.
Aimed at adults aged 18 to 75 with a confirmed BMPR2 gene alteration.
Participants continue taking their normal PAH medications throughout the study.
Led by pulmonary hypertension experts at Royal Papworth Hospital NHS Foundation Trust.
Participation is voluntary, with close health monitoring and regular check-ups.

Who may be eligible?

This trial is open to adults aged between 18 and 75 who have been diagnosed with pulmonary arterial hypertension linked to a known change in their BMPR2 gene. To join, your general health and your current PAH treatment must have been steady and unchanged for at least one month before screening, and you must weigh at least 40 kg (around 6 stone 4 pounds).

You will not be able to join if you have certain other significant health conditions. These include severe kidney or liver disease, active infections like tuberculosis or hepatitis B, severe anaemia, or bleeding problems like stomach ulcers. People who have had a heart attack within the last three months are also unable to take part.

Finally, because the study is testing specific drug actions, you cannot participate if you are already taking certain biological immune therapies (such as TNF blockers), if you take the study drugs already, or if you have had an allergic reaction to these medicines in the past.

Could this study suit you?

Answer these quick questions to see if you may be eligible. This is a guide only — the research team makes the final call.

I am aged between 18 and 75.
I weigh at least 40 kg (6 stone 4 lbs).
I have pulmonary arterial hypertension (PAH) with a known BMPR2 gene change.
My current PAH medicines have stayed the same for at least the past month.
I do not have severe kidney disease, severe liver disease, or active tuberculosis/hepatitis.
I have not had a heart attack in the last 90 days.

Answer every question to see your result.

What does participation involve?

If you decide to take part, you will continue taking all your usual prescribed PAH medicines. You will be placed into a treatment group by chance, like flipping a coin. You will receive either one of the two study drugs (hydroxychloroquine or glycerol phenylbutyrate) or a matching dummy treatment (placebo), which may come as a tablet or liquid. Neither you nor your doctor will choose which group you are in.

Throughout the study, you will have regular hospital check-ups with the research team. At these visits, doctors will monitor your health using heart tracings (ECGs) and standard blood tests. The study team will track how your body handles the medicine and check for any improvements or side effects. The entire trial is running across several years, but your study team will explain exactly how many visits you will need and over what timeframe before you agree to join.

Potential risks and benefits

Taking part in this study may not directly improve your own health, but the findings could help doctors develop much better treatments for people with PAH in the future. As with any trial, there are some minor risks. Having blood taken can cause brief pain, slight bruising, or faintness. Heart tracings use sticky pads that can sometimes irritate the skin or cause mild pulling when removed. The study medicines are already widely prescribed in the UK, but they can still cause side effects, which your trial doctor will explain in detail and monitor closely. Joining is completely your choice, and you can withdraw at any time without your regular NHS care being affected.

Locations (6)

Royal Papworth Hospital
Approximate
Cambridge, England
Golden Jubilee National Hospital
Approximate
Clydebank, Scotland
Royal Free London NHS Foundation Trust
City only
London, England
Royal Hallamshire Hospital
Approximate
Sheffield, England
Freeman Hospital
Approximate
Newcastle upon Tyne, England
Royal Brompton Hospital
Unverified
London, England

Common questions

Will I have to stop taking my usual PAH medication?

No. You will continue to take your regular PAH treatments exactly as prescribed. The study medicine or placebo is added to your normal care.

What is a placebo and why is it used?

A placebo is an inactive treatment that looks identical to the real medicine. It helps researchers prove whether any health changes are genuinely caused by the study drug rather than by chance.

Are the study drugs safe?

Both hydroxychloroquine and glycerol phenylbutyrate are already approved and prescribed in the UK for other conditions. While all medicines carry a risk of side effects, your health will be watched very closely by the research team.

How do I know if I have the BMPR2 gene change?

Your pulmonary hypertension specialist can tell you if you have had genetic testing for BMPR2. If you are unsure, your doctor can check your records or discuss testing options.

Can I leave the study if I change my mind?

Yes. Taking part is completely voluntary. You are free to leave the trial at any point, and your normal NHS medical care will continue as usual.

How to find out more

Ellen Temple-Jones

ellen.temple4@nhs.net +44 (0)1223 639809 Official trial record

Always speak to your GP or specialist before deciding to take part in a study.