NIH Funds SLU Research of Possible Treatment for Drug-Resistant TB
Saint Louis University is leading a multi-national clinical trial of what could become
a regimen for drug resistant tuberculosis (TB) that does not require injectable medications.
The project is funded by a $6.4 million task order from the National Institute of
Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health
Daniel Hoft, M.D., Ph.D., director of Saint Louis University’s Division of Infectious
Diseases, Allergy & Immunology, is the principal investigator for the trial.
The research grew out of the NIH’s commitment to finding new treatments for infections
that no longer respond to commonly prescribed antibiotics and can turn deadly, a worsening
problem that poses a critical public health risk.
TB causes more deaths world-wide than any other infectious disease, including HIV.
One quarter of the world’s population is thought to be infected with the bacterium
that causes TB and more than 10 million people develop TB each year, resulting in
close to 2 million deaths annually.
TB can become resistant to drugs such that none of the available first-line therapies
can kill the bacteria. This can occur when patients don’t take all of their TB drugs,
get the wrong dose, take them irregularly or have medicines of poor quality.
A form of TB known as multi-drug resistant (MDR)-TB is a growing health threat, with
about one half million persons diagnosed with this form. Health officials believe
the problem could be significantly larger and estimate 80 percent of those who have
MDR-TB are not diagnosed and treated. They unknowingly spread their infection to others
before it usually kills them. In addition, as MDR-TB becomes increasingly unresponsive
to medicines, patients have fewer and fewer treatment options.
Currently, patients with MDR-TB typically take five to seven drugs for up to 24 months,
coupled with an injected aminoglycoside antibiotic, for six months. This combination,
particularly because of the antibiotics that need to be injected, is very painful
and can cause hearing loss and kidney problems that make it difficult for the patients
to complete treatment.
Furthermore, since injections have to be provided by trained medical professionals,
patients have to be seen in skilled health care facilities that are often not available
in resource limited countries where drug resistant TB is a problem.
Although relatively uncommon in the United States, the problem of MDR-TB may worsen
in America as residents travel to countries where the infection is present and bring
it home, Hoft predicts.
“We already have had MDR-TB in the U.S., and if we don’t pay attention to it, the
problem will get a lot worse,” Hoft says.
Therapy for MDR-TB in the U.S. can be grueling, disruptive and costly. While treatment
of drug sensitive TB costs about $18,000, MDR-TB can cost more than $494,000, according
to the CDC.
“If the oral regimen we are studying works, it could be a game changer for treating
drug-resistant TB, especially in developing countries,” Hoft said. “Ultimately, we
need new treatments for drug-resistant TB that are shorter, safer and better tolerated
by patients, and specifically do not require daily injections.”
Saint Louis University, a member of NIAID’s network of Vaccine and Treatment Evaluation
Units (VTEUs), is partnering with Aurum Institute in Johannesburg, South Africa, the
University of Maryland VTEU and Makerere University in Kampala, Uganda, for the phase
4 clinical trial.
Study participants will be recruited in South Africa and Uganda, where MDR-TB is prevalent
and clinical data will be analyzed by Saint Louis University and University of Maryland.
Researchers will study two groups of volunteers -- those who receive the standard
therapy for MDR-TB and those who receive a regimen that substitutes an oral medication
named delamanid for the shot. In both groups, the efficacy and safety of the tested
medications will be analyzed.
Delamanid was recently approved by the FDA to add to the therapy of MDR-TB in patients
who have no other treatment options. It works by a different mechanism than other
currently used drugs, which could help solve the problem of drug-resistance by attacking
the TB bacterium on a different front.
“If we can replace the injectable antibiotics with an oral drug with similar or better
safety and efficacy, it will transform the field, likely increasing treatment completion
rates and reducing the likelihood of further drug resistance developing,” Hoft says.
Established in 1836, Saint Louis University (SLU) School of Medicine has the distinction
of awarding the first medical degree west of the Mississippi River. The school educates
physicians and biomedical scientists, conducts medical research, and provides health
care on a local, national and international level. Research at the school seeks new
cures and treatments in five key areas: infectious disease, liver disease, cancer,
heart/lung disease, and aging and brain disorders.
SLU is one of nine Vaccine and Treatment Evaluation Units selected in 2013 by NIAID
to study vaccines and treatments of the future that will protect people from infectious
diseases and emerging threats. The project is funded under Contract No. HHSN272201300021I.
The federal government has funded vaccine research at SLU since 1989. This is SLU’s
first international treatment trial and builds on their previous work in developing
vaccines to finding new treatments for infectious diseases.
To learn more about the vaccine research being conducted at Saint Louis University,