Epidermolysis bullosa – Clinical Trial Feasibility
Epidermolysis bullosa (EB) is a rare group of genetic disorders that cause the skin to be very fragile and to blister easily. It is a rare disease, and the condition was brought to public attention in 2004, in the UK through the Channel 4 documentary. It appears in many kinds of forms, and these forms are categorized differently.
All of these forms of EB have common typical characteristics. These are as follows
- Blisters and skin erosions may form in response to minor injury or friction such as rubbing or scratching.
- In mild cases, blistering may primarily affect the hands, feet, knees, and elbows.
- Severe cases of this condition involve widespread blistering that can lead to vision loss, disfigurement, and other serious medical problems.
EB is quite notorious in terms of its prevalence. Some facts about it are
- 20 per million live births are estimated to be diagnosed with EB.
- 9 per million people in the general population have the condition.
- Of these cases, approximately
- 92% is epidermolysis bullosa simplex (EBS),
- 5% are dystrophic epidermolysis bullosa (DEB),
- 1% are junctional epidermolysis bullosa (JEB), and 2% are unclassified.
- The incidence and prevalence of the disease in the United States are approximately 1/53,000 live births and 1/125,000 respectively and similar estimates have been obtained in some European countries.
- The disorder occurs in every racial and ethnic group and affects both sexes. 
Complications of epidermolysis bullosa may include:
- Infection, as blistering skin is vulnerable to bacterial infection.
- Sepsis occurs when bacteria from a massive infection enter the bloodstream and spread throughout the body.
- The fusion of fingers and changes in the joints.
- Problems with nutrition as blisters in the mouth can make eating difficult and lead to malnutrition and anemia.
- Dental problems
- Skin cancer. Adolescents and adults with certain types of EB are at high risk of developing a type of skin cancer known as squamous cell carcinoma.
- Death, survival also may be threatened because of blistering, which hamper their ability to eat and breathe. Many of these infants die in childhood. 
Clinical trial feasibility was assessed with sites/investigators from USA, India, South Africa, Australia, Denmark, Norway and Canada for one trial and with site/investigator from USA for second trial. [See below for more details]
Researchers classify dystrophic epidermolysis bullosa into three major types. Although the types differ in severity, their features overlap significantly and they are caused by mutations in the same gene.
Epidermolysis bullosa simplex
- It typically affects the hands and feet and is inherited in an autosomal dominant manner, affecting the keratin genes KRT5 and KRT14.
- In this form of EB, blisters are formed at the site of rubbing, usually, heal without scarring.
Junctional epidermolysis bullosa
- Junctional EB is an inherited disease affecting laminin and collagen, characterized by blister formation within the lamina Lucida of the basement membrane zone and is inherited in an autosomal recessive manner.
- A baby with this condition may develop a hoarse-sounding cry from continual blistering and scarring of the vocal cords.
- It also presents with blisters at the site of friction, especially on the hands and feet, and has variants that can occur in children and adults.
- Less than one person per million people is estimated to have this form of epidermolysis bullosa.
Dystrophic epidermolysis bullosa
- Dystrophic epidermolysis bullosa (DEB) is one of the major forms of EB and is an inherited variant affecting the skin and other organs.
- “Butterfly children” is the term given to those born with the disease as their skin is seen to be as delicate and fragile as a butterfly’s wings.
- DEB is caused by genetic defects (or mutations) within the human COL7A1 gene causing mutations that can be either autosomal dominant or autosomal recessive.
- Epidermolysis bullosa pruriginous and Albopapuloid epidermolysis bullosa (Pasini’s disease) are rare subtypes of this disease. 
Signs and symptoms
Signs and symptoms vary depending on the type, but commonly include:
- Fragile skin that blisters easily, especially on the hands and feet
- Nails that are thick or don’t form, thickened skin on the palms and soles of the feet
- Blisters inside the mouth and throat
- Scalp blistering, scarring, and hair loss (scarring alopecia)
- Thin-appearing skin (atrophic scarring) and Tiny white skin bumps or pimples (milia)
- Dental problems, such as tooth decay from poorly formed enamel and difficulty in swallowing (dysphagia)
- Itchy, painful skin. 
Epidermolysis bullosa can be diagnosed based on the appearance of the affected skin however laboratory tests may confirm the diagnosis and include,
- Skin biopsy for immunofluorescent mapping: a small sample of the affected skin is examined with a microscope and reflected light to identify the layers of skin involved. This test also identifies whether the proteins needed for skin growth are functioning.
- Genetic testing. Genetic testing is sometimes used to confirm the diagnosis because most forms of epidermolysis bullosa are inherited.
- Prenatal testing. Families with a history of epidermolysis bullosa may consider prenatal testing and genetic counseling. 
Treatment should aim to:
- Avoid skin damage
- Improve the quality of life and
- Reduce the risk of developing complications, such as infection and malnutrition.
There’s currently no cure for epidermolysis bullosa (EB), but treatment can help ease and control symptoms.
An important part of the children’s treatment plans will be about how to prevent trauma or friction to children’s skin to help reduce the frequency of blistering. This advice will vary depending on the type of EB and the severity of symptoms.
The advice may include:
- Avoid walking long distances, which may cause blisters to form on the soles of feet.
- Avoiding everyday knocks, bumps, and scratches.
- Parents to change the way they lift the child.
- Keeping children as cool as possible in warm weather.
- Avoiding clothes that fit tightly or rub against the skin to avoid blistering.
Other advice is related to skincare, infections, pain relief, dental care, nail care, eye care, and feeding, and nutrition.
Generally, surgery may be required to treat some complications that can arise in cases of EB.
The different types of surgery are,
- When fingers and toes have become fused together by scar tissue, creating a ‘mitten’ effect, surgery may be required to separate them.
- If the esophagus has become narrowed by scarring, surgery may be required to widen it
- If poor weight gain and reduced growth have occurred due to the symptoms of EB make eating difficult or impossible, surgery is done to implant a feeding tube.
Research in EB
A great deal of research is being carried out to find a cure or at least more effective treatments for EB.
Areas of research include:
- Applying proteins directly to the skin to prevent the layers of skin from becoming unstuck.
- Adding ‘corrected’ copies of certain genes to badly affected areas of skin and try to regulate the production of skin cells.
- Adding a type of cell known as fibroblasts to the skin to strengthen it.
- Using bone marrow transplants to stimulate the production of healthy skin cells.
- Identifying medication that can improve and accelerate the process of wound healing.
Initial results in all of these areas have been promising, but it may take several years until researchers come up with safe and effective treatments.
Total clinical trials registered around the world on EB are 79, with the major number of trials at medical centers and sites located in the United States (48), France (18), UK (10), Austria (10), and Australia (6).
The ongoing clinical trials around the globe are 27, with major trials in the United States (24), UK (3), Austria (5), France (5), and Australia (1).
[Data as on Sep-20]
Epidermolysis bullosa Global Clinical Trial Feasibility on CREDEVO
A clinical trial on Epidermolysis bullosa was explored at different locations. In one part, feasibility was assessed in the USA., while in another part, countries in Europe, Asia-Pac, and Africa regions were assessed for conducting this multicentric trial.
The clinical trial was evaluated in medical centers and sites located in the USA, India, South Africa, Australia, Denmark, Norway, and Canada.
- The primary objective of the trial is to assess the efficacy of safety as a secondary objective.
- The inclusion criteria for the study was, male or female at least 12 years of age (for Cohort 2) and at least 6 months of age to 11 years (for Cohort 3) at the screening.
- The subjects who have EBS lesions that are infected (need antimicrobial therapy) were excluded.
- Clinical trial feasibility was assessed with sites/investigators from the USA, India, South Africa, Australia, Denmark, Norway, and Canada for one trial and with site/investigator from the USA for the second trial.
- Feedback, from sites/investigators with patient recruitment potential, varied in different countries. However, on average, the recruitment rate found in this feasibility was 7 patients / 4 months.
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