Clinical Trials News

Follicular Unit Extraction vs Older Methods of Hair Transplantation

2009-03-09T14:45:00.000-07:00

In the past, as the names of these earlier procedures indicate, undergoing a hair transplant was a painfully unpleasant process. Men with receding hairlines and balding scalps often resorted to the unnatural-looking, and often ridiculed, toupee to avoid the pain, slow healing, and scarring of a transplant.

Because of this, the hair transplant business was staggering in the late twentieth century. Surgeons knew that hair restoration techniques needed to evolve.

Thousands of bad comb-overs and strip incision scars later, the new technique that hair restoration surgeons were waiting for was finally perfected. The hair transplant community eventually embraced follicular unit extraction (FUE). Surgeons praised the method and potential patients were curious about it.

But what exactly is follicular unit extraction? And is it really more effective and beneficial than older methods of hair transplantation?

Follicular unit extraction involves the removal of small groups of hair follicles (usually between one and four) from the donor site and their reinsertion into the receptor site. These small grafts allow for equal distribution of hair in the balding area of the scalp and produce more natural-looking results. In fact, once the receptor site has completely healed, it is virtually impossible to detect that any sort of hair transplant procedure has taken place.

The differences between FUE and the older methods of transplantation are noteworthy.

Firstly, the FUE procedure is quicker and less painful than any other hair restoration technique. FUE is performed with a punch-like scalpel that cuts the skin around the follicle. This facilitates the removal of about one to four follicles from the donor area at the same time. Also, the advanced method of follicular perforation� allows the surgeon to make a shallow punch on the surrounding tissue, ensuring that the graft be released from the tissue with minimum traction and with better ease. The extracted follicles (called grafts) are then inserted into small slits that have been cut in the recipient area. These slits do not need suturing, heal quickly, and are completely undetectable once the new hair begins to grow in about seven to ten days.

Secondly, FUE is beneficial because the recovery process is much faster and less painful. In most patients, the grafts become fully secure in about eight days after surgery and the surgical wound in the donor area usually heals within one to two weeks. Some discomfort may be present, but usually analgesics like Tylenol or codeine will help. Generally, normal activity may be resumed one to two weeks after the procedure. In older methods of hair restoration, bleeding, suturing, and bandaging were parts of the long and painful recovery process.

Thirdly, 100% of hair loss sufferers are candidates for FUE. In the past, hair restoration was not as widely available to every hair loss sufferer as it is today. There were various criteria that each candidate had to meet to be eligible for a hair transplant. Such criteria included the patient's age, color and texture of hair, skin complexion, amount of donor hair available, and future hair loss projections. However, because the methods involved with follicular unit extraction are so advanced, such criteria are not much of a concern. For example, the amount of donor hair on the head is not an issue when determining candidacy because the procedure allows for the extraction of hair from other parts of the body.

Fourthly, the incidence of complication during the FUE procedure is lower than with other transplantation methods. In a study, published by Dr. Masumi Inaba, of over 150 patients treated with FUE, researchers found that patients suffered only from mild discomfort from sitting still for several hours at a time. Furthermore, only four out of the 150 patients experienced donor area shock, while two more patients experienced a more limited variety of patchy circular alopecia (hair loss). Nevertheless, all patients made full recoveries of hair transplant within five weeks.

Lastly, FUE patients recover without visible scars in the donor or recipient area. Unlike previous methods, like strip incision, where an unattractive linear scar was exposed in the donor area, FUE does not leave ugly, unbearable scars on the head. Instead, the tiny slits that are cut in the recipient area are conveniently hidden by new hair. The final result of FUE in all patients is that of a seamless, natural, healthy-looking head of hair.

For all those who are suffering from hair loss and are searching for the best method of restoring their youth, follicular unit extraction should be considered. It is a hair restoration method that discards the use of the painful linear donor incision and regards 100% of hair loss patients as proper candidates for the procedure. It is widely predicted that within the coming years, follicular unit extraction will make further advancements and become the method of choice for every hair restoration surgeon and patient.

Gold Spheres Seek And Destroy Melanoma Cells

2009-02-02T04:54:00.000-08:00

US researchers armed tiny hollow gold spheres with a highly targeted peptide so they could hunt down and get deep inside melanoma cells and then destroy them using heat converted from infra red light.

The research was the work of scientists from the University of Texas MD Anderson Cancer Center and is published in the 1 February issue of Clinical Cancer Research.

Senior author Dr Chun Li, a professor in MD Anderson's Department of Experimental Diagnostic Imaging said:

"Active targeting of nanoparticles to tumors is the holy grail of therapeutic nanotechnology for cancer."

Li said he and his team were getting closer to that goal.

Co-author, Dr Jim Zhang professor in the University of California-Santa Cruz Department of Chemistry developed the tiny gold spheres, 40 to 50 nanometres in diameter. Their hollowness allows them to penetrate cells, and they have a strong but narrow and tunable ability to absorb light at the visible and near-infrared end of the spectrum, something other metal nanoparticles don't have.

Li, Zhang and colleagues used the minimally invasive treatment on live lab mice. The method is called photothermal ablation, where target tissue is destroyed by irradatiating the target area in which the thermal material, in this case nanoparticles, but sometimes optical fibres are used, is irradiated with light which is turned into heat to destroy the surrounding tissue.

However, melanomas are not easy to treat in this way because it is hard to get the targetting metal particles to differentiate between healthy and cancerous tissue. Li and colleagues were able to do this by embedding a peptide, a small molecule made up of amino acids, in the gold nanospheres. The peptide was highly targeted, it would only bind to the melanocortin type 1 receptor, which is overly abundant in melanoma cells.

First in Cultured Cells

Li and colleagues first treated the melonoma cells in culture. When they switched on the infra-red light, the nanospheres absorbed the light and converted it to heat, which burned off the tumors (they literally got "cooked"). Infra-red light penetrates deeper into tissue than visible or ultraviolet light.

They found that the actively targeted gold nanospheres did more than eight times more damage to the melanoma tumors than the same nanospheres that were not actively targeted.

It is possible to treat cancer just using the targeted light on its own (via embedded optical fibres), but as already mentioned, melanomas are much harder because they are surrounded by healthy tissue. With the highly targeted gold nanospheres as a way to focus the light, Li and colleagues were able to use 12 per cent of the dose required, which is more likely to spare surrounding healthy tissue.

The injected nanospheres are small enough to get right inside the melanoma tumor and attach themselves to the cancer cells' blood supply. Using fluorescent tagging on the nanospheres that they tested on the cultured melanoma cells, Li and Zhang and colleagues were able to show that the targeted nanospheres were drawn right into the cells through the cell membrane while the untargeted ones were not.

When they irradiated the treated cultures, the researchers found that most cells containing the targeted nanospheres died, and nearly all those left where damaged beyond repair. But this did not happen with the untargeted nanospheres, only a very small fraction of cells treated with them died.

Also, irradiation with near-infrared light alone, or treatment with nanospheres alone without light, had no effect on the cells.

It was therefore the combination of highly targeted nanospheres and the irradiation that had the maximum effect of killing targeted cancer cells.

Then in Live Mice

In the live mice, fluorescent tagging showed that the untargeted nanospheres gathered near the tumor's blood vessels whereas the targeted ones penetrated into the tumor and were found spread around inside it.

A common problem with using nanoparticles is that the body sends foreign matter to the liver and spleen for destruction. Most of the targeted nanospheres stayed in the tumor, with some found in the liver and spleen. But most of the untargeted nanospheres gathered in the spleen, then the liver and then the tumor. The researchers said this showed the importance of targeting the nanospheres more selectively.

Li said:

"There are many biological barriers to effective use of nanoparticles, with the liver and spleen being the most important."

When they irradiated the mice with the near infrared light, those that had been injected with targeted nanospheres, had nearly 66 per cent of their tumors destroyed. This compared with only 7.9 per cent tumor destruction in the mice that had only been injected with untargeted nanospheres.

The researchers were able to measure the tumors by using tagged glucose (F-18-labelled). This shows up on a PET scan. Tumors treated with targeted nanospheres did not light up very much, showing there was little metabolized tagged glucose in them.

Clinical Implications

While the findings of this study show implications for the treatment of melanomas, Li said they were proof of principle for other cancers too.

"Receptors common to other cancers can also be targeted by a peptide-guided hollow gold nanosphere," said Li.

"We've also shown that non-invasive PET can monitor early response to treatment," he added, explaining that the hollow nanospheres are also made with pure gold, which has a long history of safe use in medicine with few side effects.

The National Cancer Institute Alliance for Nanotechnology in Cancer, the John S. Dunn Foundation, and the U.S. Department of Defense paid for the study.

Co-authors with Zhang, and Li were: Wei Lu (first author), Chiyi Xiong, Guodong Zhang, Qian Huang and Rui Zhang, all from MD Anderson's Department of Experimental Diagnostic Imaging.

RegeneRx Completes Patient Enrollment Of First Phase II Clinical Trial

2008-08-27T13:55:00.000-07:00

Regenerx Biopharmaceuticals, Inc. (AMEX:RGN) announced that it completed enrollment of its first of four ongoing Phase II clinical trials. The trial is a double-blind, placebo-controlled, dose-escalating clinical trial evaluating the safety and efficacy of the Company's topical drug candidate, RGN-137, in seventy-two patients with pressure ulcers who are being treated for up to 84 days or less if fully healed. RGN-137 is a formulation of thymosin beta 4 specifically for topical delivery to dermal wounds. Twenty-two wound care centers and hospitals in the United States have participated in the study. The Company expects to report results in the fourth quarter of 2008.

"Clearly, we are excited about reaching this important milestone. While each of our Phase II trials will stand on its own and give us valuable information in separate medical indications, this trial will give us the first information on RGN-137's safety and efficacy in dermal wound healing. Currently there are no pharmacological agents approved for improving the healing of pressure ulcers and we look forward to reporting the results once they are available," stated David Crockford, RegeneRx's vice president for clinical and regulatory affairs.

Einstein's Monoclonal Antibody Shows Encouraging Results In Clinical Trial Of Novel Melanoma Treatment

2008-06-28T22:05:00.000-07:00

Image via WikipediaPain Therapeutics, Inc. recently announced the successful completion of its first clinical study utilizing a novel melanoma treatment, which the company licensed from Albert Einstein College of Medicine of Yeshiva University. The treatment consisted of dosing patients with a monoclonal antibody labeled with a radioisotope.

A research team at Einstein, led by Arturo Casadevall, M.D., Ph.D., professor and chairman of microbiology & immunology, and Ekaterina Dadachova, Ph.D., associate professor of nuclear medicine and of microbiology & immunology, developed the novel approach to treat metastatic melanoma based on targeting melanin, a skin pigment that is released from dead melanotic tumor cells, with radiolabeled monoclonal antibodies. While the antibodies seek out the released melanin and destroy human melanoma cells with a lethal dose of ionizing radiation, melanin in normal, healthy tissue is not targeted because it is inside the cells and not accessible to the radio-labeled antibody. Small animal studies have demonstrated the feasibility of this approach.

In the recent clinical study, a team of researchers in Israel administered the radiolabeled monoclonal antibody to 12 patients diagnosed with advanced melanoma. Top-line results of this Phase I study indicate this antibody binds to melanoma tumor sites, as evidenced by powerful imaging data obtained by planar scintigraphy and SPECT/CT (single photon emission computed tomography combined with computed tomography). No serious drug-related, adverse events were observed in this study.

"Our initial findings demonstrated how basic research in one area of medicine can yield unexpected benefits for an entirely different field," said Dr. Casadevall. "We didn't set out to find a cure for melanoma. Instead, the advance emerged from my study of Cryptococcus, a fungus that can cause fatal infections in people with weakened immune systems and evolved from there. It is exciting when findings take such a promising turn and we are thrilled that this first clinical study using our monoclonal antibody has met with the success that it has thus far."

"Going from the laboratory to clinical application is what we researchers strive to do so that physicians and their patients can be offered more and better options for treatment," said Dr. Dadachova. "It is among the most rewarding aspects of conducting research and we are grateful to Pain Therapeutics and our colleagues at Hadassah Medical Center for their efforts to determine how useful this treatment can possibly be. We have great hopes for further success."

The objectives of the first Phase I study were to assess safety, pharmacokinetics and dosimetry to normal organs. As a result of encouraging data in all of these areas, Pain Therapeutics plans to initiate a second study in which patients will receive increasing amounts of radioactivity delivered by the radiolabeled antibody. The radioactive doses delivered to these patients will be significantly higher than those delivered to the patients of the first study.

At the Society for Nuclear Medicine Annual Meeting in New Orleans, last week, research teams from each of the collaborating laboratories - at Albert Einstein College of Medicine (New York) and Hadassah Medical Center (Jerusalem) presented data related to Pain Therapeutics' melanoma program. This meeting is considered to be the world's most significant technical meeting focused on breakthrough developments in clinical imaging and nuclear medicine.

At the meeting, Dr. Dadachova also was presented with an award by the Society's Young Professionals' Committee. The award is given in recognition of significant contributions to the fields of nuclear medicine and molecular imaging by young researchers.

Long-Term Improvement Of Chronic Plaque Psoriasis Shown In Ustekinumab Phase 3 Data

2008-02-04T03:13:00.000-08:00

One-year data from a second double-blind, placebo-controlled Phase 3 study showed therapy with ustekinumab given every 12 weeks provided sustained, clinically meaningful improvement in the treatment of moderate to severe plaque psoriasis through one year. According to findings presented at the Annual Meeting of the American Academy of Dermatology, 87 percent of patients responding to ustekinumab 45 mg maintenance therapy and 91 percent of patients responding to ustekinumab 90 mg maintenance therapy sustained at least a 75 percent improvement in psoriasis through one year, as measured by the Psoriasis Area and Severity Index (PASI 75). Ustekinumab is a new human monoclonal antibody with a novel mechanism of action that targets the cytokines interleukin-12 (IL-12) and interleukin-23 (IL-23), naturally occurring proteins that are important in the body's regulation of immune responses and that are also believed to play a role in immune-mediated inflammatory disorders, including psoriasis.

In December 2007, Centocor announced that a Biologics License Application (BLA) had been submitted to the U.S. Food and Drug Administration (FDA) and Janssen-Cilag International NV announced its submission of a Marketing Authorization Application (MAA) to the European Medicines Agency (EMEA).

"These findings show that ustekinumab may control plaque psoriasis with as few as four injections a year," says lead study investigator Kenneth Gordon, MD, associate professor, Feinberg School of Medicine, Northwestern University, and Head of Dermatology, Evanston Northwestern Healthcare, Skokie, IL. "We are encouraged by the results seen in clinical trials to date and the hope that ustekinumab may hold for patients and the dermatology community."

The primary endpoint of the Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Trial Evaluating the Efficacy and Safety of CNTO 1275 in the Treatment of Subjects with Moderate to Severe Plaque-type Psoriasis Followed by Long-term Extension (PHOENIX 1) study examined the proportion of patients achieving at least a 75 percent improvement from baseline at week 12. Investigators reported findings from PHOENIX 1 that showed at week 12, after two doses, 67 percent of patients receiving 45 mg ustekinumab and 66 percent of patients receiving 90 mg ustekinumab achieved PASI 75 compared with 3 percent of patients receiving placebo (P<0.001 for each comparison versus placebo). Furthermore, 42 percent of patients in the 45 mg ustekinumab dosing group and 37 percent of patients in the 90 mg ustekinumab dosing group achieved PASI 90, or nearly complete clearance of psoriasis, compared with 2 percent of patients receiving placebo (P<0.001). Primary endpoint study findings from PHOENIX 1 were consistent with the week 12 primary endpoint findings reported at the World Congress of Dermatology in October 2007 from another study, the Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Trial Evaluating the Efficacy and Safety of CNTO 1275 in the Treatment of Subjects with Moderate to Severe Plaque-type Psoriasis Followed by Long-term Extension 2 (PHOENIX 2).

In the PHOENIX 1 study, subjects who received 45 mg or 90 mg of ustekinumab and consistently achieved a 75 percent improvement from baseline were randomized at week 40 to either continue treatment or switch to placebo, with levels of response to maintenance therapy measured at week 52. Of those patients who continued treatment with ustekinumab 45 mg and ustekinumab 90 mg dosing, 87 percent and 91 percent, respectively, had a sustained PASI 75 response compared with 64 percent and 62 percent of patients switched to placebo (P≤0.001 for 45 mg comparison; P<0.001 for 90 mg comparison). Also at week 40, 66 percent and 73 percent of patients achieved PASI 90 after receiving either 45 mg ustekinumab or 90 mg ustekinumab, respectively, and response rates remained stable through week 52 with continued treatment, compared with 37 percent and 38 percent of patients switched to placebo.

"The Phase 3 efficacy and safety data for ustekinumab are extremely promising and offer hope to a patient population in need of additional therapeutic options," says Kim Papp, MD, PhD, Probity Medical Research, Waterloo, Ontario, and lead study investigator.

About the PHOENIX 1 Trial

PHOENIX 1 evaluated the efficacy and safety of ustekinumab in the treatment of 766 patients with chronic plaque psoriasis. Patients were randomized to receive subcutaneously administered ustekinumab or placebo. Patients randomized to receive ustekinumab received 45 mg or 90 mg doses at weeks 0 and 4 followed by the same dose every 12 weeks. Patients in the placebo group crossed over to receive either 45 mg or 90 mg doses of ustekinumab at weeks 12 and 16 and every 12 weeks thereafter. The primary endpoint of the study was the proportion of patients achieving PASI 75 at week 12. Patients responding to ustekinumab through week 40 were randomized to either continue treatment with ustekinumab or were switched to placebo.

Through week 12 (the placebo-controlled portion of the study) the percentages of study participants experiencing at least one adverse event (AE) were comparable between the placebo group (48 percent) and the ustekinumab 45 mg group (57 percent) and 90 mg group (51 percent). Those patients experiencing at least one serious AE were reported as follows: 1 percent and 2 percent of patients receiving 45 mg or 90 mg ustekinumab, respectively, compared with 2 percent of patients receiving placebo. After the randomization at week 40, 46 percent and 49 percent of patients continuing treatment with 45 mg and 90 mg ustekinumab, respectively, experienced at least one AE, compared with 56 and 48 percent of patients switched to placebo. Serious AEs were observed in 0 and 1 percent of patients continuing treatment with 45 mg and 90 mg ustekinumab, compared with 0 and 2 percent of patients switched to placebo.