Clinical trials

What are clinical trials?

Clinical trials are medical research studies that require patient participation and aim to answer medical questions, usually concerning a new treatment for a particular disease or syndrome. This can take the form of a new drug, surgical technique or medical device, either alone or in combination with an existing treatment. However clinical trials can also investigate how genetics or environmental factors can increase the risk of developing a given condition or new screening, diagnostic or preventative methods.

In addition, clinical trials can also be observational, and aim to collect information about the symptoms and medical problems people with a particular disease have. This sort of trial is particularly useful for rare diseases, where not much is known about the disease.

What is the aim of a clinical trial?

Clinical trials test whether a new treatment or procedure is better than those currently available to patients. This involves examining the safety of the new therapy, the side effects, efficacy and overall effect on quality of life

Not all clinical trials are successful, at least in terms of identifying a new therapeutic strategy. Some may show that the new treatment being tested does not work as well as other currently available treatments, or that the combination of certain drugs does not make a difference to being treated with a single drug. However, this knowledge is extremely valuable to researchers and clinicians, and ultimately patients, as it helps direct new lines of research and the development of new strategies for treatment.

  • Phase I: tests the safety and the best way to administer the new treatment in a small number of people, usually around 20-100 healthy volunteers, although occasionally patients are also recruited.
  • Phase II: tests the effectiveness and side effects of the treatment, sometimes compared to a placebo, in a larger number of  people who would benefit from a new treatment e.g. a new drug for renal cancer in people with BHD, as opposed to healthy volunteers.
  • Phase III: tests the effectiveness and safety of the treatment compared to placebo or another treatment in a large group of patients, this can be hundreds or thousands of people. If a treatment passes Phase III, it can be approved for general use.
  • Phase IV: occurs in a “real-world” setting once the treatment is freely available. This phase typically determines the long term risks and benefits of the treatment when it is used in the general population.

The best way to accurately determine how well a new treatment works is to split the patients into two groups at random and to give patients in one group the new treatment and patients in the other a “control” treatment. How the two groups respond to their respective treatments can then be compared. This is known as a randomised controlled trial and usually happens in Phase III, but can also happen in phase II.

In a placebo controlled trial, the control group is given a dummy treatment. Alternatively, patients in the control group can be given the best currently available treatment. If the trial is investigating the effect of combining particular drugs (e.g. a new drug and an already approved drug), this is often compared to treatment with the already approved drug alone. Given the ethical implications of giving patients a fake treatment, placebo controlled trials are increasingly rare, meaning that in the majority of clinical trials, all participating patients will receive an effective treatment.

Many trials are performed “blinded”, which means that during the trial, the patient does not know which treatment they are getting. Some trials are “double-blinded” which means that neither the doctor nor the patient know which treatment the patient is getting. This is to ensure that the results obtained from the trial are objective.

In order to participate in a trial, you must give informed consent. This means that a patient can only take part once a healthcare professional has explained the aims, procedures, benefits and risks of the study and the patient has demonstrated that they have fully understood this information and give their consent to participate. In some cases it may be possible for someone else to give informed consent on a patient’s behalf, for example when a parent consents for their child to take part in a clinical trial.

Recruitment and access to clinical trials will vary greatly depending on the type of study, the phase of the trial, where the trial is located and where you are located. Clinical trials for rare diseases are often complicated by the small populations affected and as such it can be difficult to recruit enough volunteers, particularly for phase III. The most common way of entering a clinical trial is to be referred by your doctor. Therefore, if you find a trial you are interested in joining, you should talk this through with your doctor.

Additionally, you could also contact the trial coordinator to discuss if you are eligible to participate. Please do bear in mind that eligibility for clinical trials is generally quite strict, so even if you would like to participate in a trial, it may not always be possible.

Clinical trials are not without a degree of risk. You should always consult your doctor about participating in a clinical trial.

If you are interested in taking part in a clinical trial, more information about trials currently in progress can be found at the following sites:

BHD Clinical Trials

There are a number of clinical trials that individuals with BHD syndrome are eligible for:

This trial aims to fully characterise the types of kidney cancer caused by BHD Syndrome and to calculate the risk BHD patients have of developing kidney cancer. Patients on this trial will undergo a number of non-invasive scans and tests on an outpatient basis and one the studies are complete will receive counselling about the findings and recommendations. This study is open to all BHD patients worldwide.

This is an observational study aiming to investigate the clinical symptoms of familial kidney cancers and to determine if there is a link between a given gene mutation and disease manifestation and phenotype including presenting age and rate of recurrence. This study is open to all those with a family history of kidney cancer, including those with BHD. Enrolled patients will undergo periodic clinical assessment at a medical center Bethesda, MD, USA.

This is multi-patient database for patients with Von Hippel-Linday Disease, Hereditary Leiomyomatosis, SDHB gene mutation and BHD.  To provide the patient community and researchers more information about these conditions.

This is a study looking at the genetics of individuals at risk of developing kidney cancer. It involves a blood sample and questionnaire and recruitment ends in March 2022.

Past BHD Clinical Trials 

This trial tested whether a topical Rapamycin treatment was effective in reducing the size and/or number of fibrofolliculomas. The trial did not find that Rapamycin was an effective treatment for fibrofolliculomas. For more information, please read our news itemblog post and lay summary about the trial’s results.

This is an observational study to assess the safety of air travel in patients with BHD syndrome via a questionnaire. Secondary aims of this study include further characterization of the clinical aspects of disease and to establish a contact registry for these patients, in order to facilitate future studies. A paper titled ‘Spontaneous Pneumothoraces in Patients with Birt-Hogg-Dubé Syndrome’ was published with the results of the trial.

Other BHD Trials 

This is a phase I trial aiming to assess the prevalence of BHD among patients with spontaneous pneumothorax. Patients who were treated for primary spontaneous pneumothorax in the Rijnstate hospital, Netherlands are to be included. Enrolled patients will be invited for a one-time visit to the out-patient clinic. Patients will be asked for a blood sample to determine pathogenic FLCN mutations and a pulmonary CT scan for evaluation of presence of lung cysts. The Trial is ongoing but no longer recruiting.

This is a phase II trial to determine if Everolimus is safe and effective in BHD patients with renal cancer. Patients were asked to take one tablet daily and keep a diary of symptoms, with additional physical examinations and clinical tests as required. The trial was terminated as there were not able to recruit enough patients into the trials.

Publication date: December 2014
Review date: May 2021