Clinical Trial and Other Important Definitions

Adaptive design – Type of trial design in which it is preplanned when data will be looked at and reviewed (interim review) and changes may occur to the study design based upon the interim review.  This may help decrease time in between trials or phases.

Biomarker – A marker of disease or response to therapy that might be used to diagnose ALD, monitor disease progression, or monitor treatment effectiveness; they may take the form of molecules in body fluids or changes on imaging tests, such as MRI.

Biorepository – A collection of stored biological samples.  Carefully collected and stored samples are critical for scientists to conduct research on disease mechanisms, causes, and for developing disease biomarkers.  They are the foundation of research.

Cerebral ALD – One of the major phenotypes associated with the ALD gene mutation. Patients with cerebral ALD develop severe, progressive brain inflammation that leads to disability and death if untreated. Hematopoietic stem cell transplant is the standard treatment for cerebral ALD, but must be implemented very soon after the onset of the brain inflammation.  Cerebral ALD affects more than 60% of ALD males (it almost never affects females with the ALD gene) and is the most destructive phenotype of ALD.

Cerebrospinal fluid (CSF) – Clear colorless fluid that occupies space in and around the brain and spinal cord to protect them from injury; an important source of testing to identify biomarkers.

Cohort – group of people sharing common factors e.g. age, gender, diagnosis.

Cord blood –  blood that comes from a newborn’s umbilical cord and is collected immediately after birth. Once the umbilical cord has been clamped and cut, the remaining blood in the umbilical cord is drawn into a collection bag.  Cord blood is a source of hematopoeitic stem cells (HSCs), which create blood and immune cells.

Crossover-design – Type of trial design; a randomized, trial where group one receives treatment A and group two receives treatment B, then at a predetermined point the groups switch treatments.

Dementia – a group of symptoms characterized by a decline in cognitive (thinking) functioning that is severe enough to interfere with activities of daily living.

Double-blind – Trial design feature; neither the researchers nor the research participants know which participants are getting active medication and which are getting placebo.  At the end of the trial, the “blind is broken,” and the researchers and patients find out who received active treatment.

Electromyography (EMG) – An EMG involves a series of tests, including both nerve conduction studies (NCS) and needle electromyography (EMG), that measure nerve signaling and muscle response.

Genotype – The genetic make-up of a cell or organism.

Hematopoietic stem cells (HSCs) – Stem cells that are derived from another individual’s bone marrow and then administered to a different person from which they were taken. These cells are able to mature into different cell types.

Informed consent – A person’s voluntary agreement to participate in research based on adequate knowledge and understanding of relevant information.  Informed consent is documented in the informed consent form.  Before signing a form, participants should always be sure to ask as many questions as needed to feel fully informed.

Interventional trial – Type of a trial; a clinical research study in which exposure to the potential therapy being tested, (e.g. a drug), is assigned; used to determine the effectiveness of a treatment or intervention.

Interventional trial with drugs and a placebo – Compares the effect of the treatment to the effect of a placebo; One group receives the treatment, the other receives the placebo. Everything else is held the same between the two groups, so that any difference in their outcome can be attributed to the active treatment; considered the “gold standard” because this design allows statistical evaluation of an effect; the FDA typically requires 2 controlled trials showing benefit before approving of new treatments.

In vitro – In an artificial environment outside the living organism, such as a test tube.

In vivo – In a living organism, such as a mouse or human.

Loes MRI Score – A standardized scoring system that communicates the severity of brain injury in the cerebral demyelinating form of ALD in the form of a single number ranging from 0 to 34.

Lumbar puncture – Procedure performed in an exam room used to collect cerebrospinal fluid (CSF).  The patient lies on his/her side or sits upright during the procedure.  Numbing medication is used to numb the skin.

Neuroprotective – Treatments that may protect the nervous system against weakening, illness, or degeneration.

Neurologic Function Scale (NFS) or Raymond Scale – A clinical scoring system designed by Gerald Raymond and his colleagues at the Kennedy Krieger Institute to capture the typical neurologic progression of disease boys with cerebral ALD across 15 functional domains.

Non-invasive – Non-surgical procedure, non-phlebotomy.

Observational study – Type of a trial in which enrolled participants are observed.  Outcome measures (e.g. measures of strength or function) may be part of the observation.  No treatment is given; often used to learn about trends of symptoms or the course of a disease.

Open-label design – Trial design feature; both researchers and patients know that the patient is receiving an active treatment no placebo.

Open-label extension – Trial design feature; at the conclusion of a randomized, placebo-controlled trial, all participants are invited to take the active study drug, regardless of whether they were on active study drug or placebo.  Typically researchers continue to gather information from participants during the open-label phase.  If a drug is shown to be ineffective or unsafe, the open-label extension is closed.

Parallel design – Type of trial design; a randomized, interventional trial, in which one group receives only treatment A and another group receives only treatment B.  In contrast to Crossover design (See Definition)

Paraplegia – Paralysis from illness or injury that leads to loss of the use of the legs.

Pharmacodynamics – refers to the effects of a drug on its target in the body.  As an example, the pharmacodynamic effect of a cholesterol-lowering drug is measured by testing cholesterol levels in people taking the drug.

Pharmacokinetics – refers to the level of a drug in the body and the speed at which the body metabolizes and eliminates a drug.  As an example, the pharmacokinetics of a drug can be followed by drawing blood to check the level of the drug in the blood.

Phenotype – A physical manifestation of genetic condition. Several phenotypes may occur in association with a single genotype, as is seen in ALD, where siblings with the same genotype have different phenotypes (e.g. one brother may have cerebral ALD while the other has AMN).

Placebo – An inactive substance that looks and tastes like the tested drug but has no known effect on the disease under study (e.g. ALD/AMN); sometimes called a “sugar pill” or “dummy.”

Placebo-controlled trial – Type of trial design; participants are assigned to one of two (or more) groups, either receiving active therapy (sometimes at different doses) or placebo. Everything else is held the same between groups, so any difference in their outcome can be attributed to the active treatment.

Protocol – A study plan on which all clinical trials are based. The plan is carefully designed to safeguard the health of the participants as well as answer specific research questions. A protocol describes what types of people may participate in the trial; the schedule of tests, procedures, medications, and dosages; and the length of the study. While in a clinical trial, participants following a protocol are seen regularly by the research staff to monitor their health and to determine the safety and effectiveness of their treatment.

Randomized – Participants are randomly assigned to one group or the other; each participant has just as much of a chance as any other participant to receive either the treatment or placebo.

Selection design – Type of trial design; may speed the search for effective drugs through simultaneous testing of multiple drugs, usually without a placebo; allows for rapid development through researchers choosing the most effective and safest for further trials.

Time to event – Trial design feature; In placebo-controlled trials using this design, participants are assigned to a treatment
group (active study drug or placebo) and followed in the study until they reach a pre-specified “event” (e.g. “event” may be defined as a decrease in the Loes MRI Score).  If a participant reaches this “event,” he/she will enter an open-label extension (see definition).

Trial Phase – Experimental therapies, including drugs, pass through 3 phases of trials on their way to FDA, EMA or other regulatory authority approval.  Additional trials may be required post-approval.

Phase I: Researchers test a new drug or treatment in a small group of people for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.

Phase II: The drug or treatment is given to a larger group of people to see if it is effective and to further evaluate its safety.

Phase III: The drug or treatment is given to large groups of people to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.

Phase IV: Studies are done after the drug or treatment has been marketed to gather information on the drug’s effect in various populations and any side effects associated with long-term use.