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Ask Stanford Med, Chronic Disease, Clinical Trials, Patient Care

Ask Stanford Med: A focus on scleroderma

Ask Stanford Med: A focus on scleroderma

Melissa Warde’s life was forever changed 21 years ago when, at the age of 15, she was diagnosed with scleroderma. At the time, little was known about the chronic connective tissue disease, which involves the hardening and tightening of the skin and fibers that provide the framework and support for the body. “I knew from that day forward, I could sit back and wait for the disease to progress or I could, to the best of my ability, work to control the disease within myself,” Warde said during an Ask Stanford Med Google+ Hangout last week. “I knew I had to have a cheerful disposition, despite the tragedy that I was dealt, and of course having a positive attitude really helped me to focus on the winnings of life.”

During the live conversation, Warde was joined by Lorinda Chung, MD, director of the Scleroderma Center and co-director of the Multidisciplinary Rheumatologic Dermatology Clinic at Stanford, and Karen Gottesman, patient services director for the Scleroderma Foundation of Southern California, for a panel on scleroderma research and progress being made to enhance patients’ quality of life.

Chung opened the discussion with an overview of recent modifications to the disease criteria used in diagnosing scleroderma. Since no two cases of scleroderma are alike, the disease can often be difficult to diagnosis. However, early detection (.pdf) is critical for improving patient outcomes. Under the new criteria, physicians are directed to look for symptoms such as puffy fingers, capillary changes in the nail folds or Raynaud’s disease, which is present in 90 percent of patients with systemic sclerosis. Chung said:

Previously, patients really had to have significant, pretty obvious, skin tightening in order to meet the classification criteria. Or have interstitial lung disease or pulmonary fibrosis, which is scarring in the basis of the lungs, in order to meet the criteria.

These new classification criteria will enable rheumatologists, who may be less experienced in scleroderma, to detect early signs and then refer [patients] appropriately for an accurate diagnosis.

Following Chung’s update on the modifications to the disease criteria, Gottesman spoke about how patients can mange stress related to learning they have a rare, incurable disease and continue living life to the fullest. She advised:

Really learn to be your own advocate. Part of that means educating yourself, not only on all the different aspects of the disease, but also on what type of scleroderma you have so you are aware of possible symptoms that come up.

I think what scares a lot of patients and is really stressful is when you hear of a disease that doesn’t have a cure. But you have to keep in mind that there are hundreds of diseases without cures and we have a lot of treatments in the toolbox to treat the symptoms. At the end of the day you have to learn to co-exist with the disease and that process is really different for every single patient.

Being a proactive patient, Gottesman said, also means being a compliant patient and following through on properly taking any prescribed medications, completing physician recommended tests and other instructions from health-care providers. She said, “If you have a different game plan in mind, then you really need to be upfront [with your doctor] about what it is you need and what you think you want to do, so that you can communicate. That will help you in the long run.”

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Clinical Trials, NIH, Nutrition, Obesity, Research, Stanford News

Stanford seeks participants for weight-loss study

Stanford seeks participants for weight-loss study

Should diets come in different shapes and sizes? Stanford researchers are exploring that question and are seeking participants for a year-long weight-loss study that aims to understand why people may respond differently to the same diet. Titled “One Diet Does Not Fit All,” the study will examine how factors such as genetic influences and eating and sleeping habits have an impact on a diet’s effectiveness.

From a release:

Participants will be assigned randomly to either a very low-fat or very low-carbohydrate diet for 12 months. They will be required to attend weekly classes at Stanford for the first three months, once every other week for the following three months, and once a month for the remainder of the study. Participants must also be willing to have fasting blood samples drawn four times during the 12-month period and participate in online and written surveys. They will receive all test results at the end of the study.

The study is part of a five-year project funded by the National Institutes of Health and the Nutrition Science Initiative. Following an enrollment last year of 200, this spring researchers hope to enroll at least 135 men and women (pre-menopausal only) between the ages of 18 and 50 who are overweight or obese and are generally in good health.

For a complete list of inclusion criteria, click here. To determine eligibility for this study, complete a brief online survey. For more information, contact Jennifer Robinson at nutrition@stanford.edu.

Previously: How physicians address obesity may affect patients’ success in losing weight, To meet weight loss goals, start exercise and healthy eating programs at the same time, The trouble with the current calorie-counting system, Smaller plates may not be helpful tools for dieters, study suggests and Losing vitamins – along with weight – on a diet

Clinical Trials, Nutrition, Science, Stanford News

Bad news for pill poppers? Little clear evidence for Vitamin D efficacy, says Stanford’s John Ioannidis

Bad news for pill poppers? Little clear evidence for Vitamin D efficacy, says Stanford's John Ioannidis

Vitamin DVitamin D is a darling of the supplementation world. Deficiencies in the vitamin have been blamed for all manner of ailments, including diseases of the skeletal system, autoimmunity, infections and cancer.

Now researchers from the University of Edinburgh, Imperial College London and the University of Ioannina School of Medicine in Greece have analyzed 107 systematic literature reviews and 161 meta-analyses regarding vitamin D supplementation or levels in blood plasma and the occurrence of 137 various medical outcomes. They’ve published their findings in today’s issue of the British Medical Journal, where they wrote:

In conclusion, although vitamin D has been extensively studied in relation to a range of outcomes and some indications exist that low plasma vitamin D concentrations might be linked to several diseases, firm universal conclusions about its benefits cannot be drawn.

In particular, the researchers found that the evidence does not support a role for vitamin D in increasing bone mineral density or reducing the risk of falls and fractures in older people. As senior author and Stanford study design expert John Ioannidis, MD, DSc, explained to me in an e-mail:

Vitamin D has been evaluated in thousands of studies in terms of its relationship to at least 137 health outcomes. We hope that systematic consideration of the available evidence will help avoid hot debate about health decisions involving vitamin D  that have mostly depended on speculations rather than evidence to-date.

Rather than writing off vitamin D altogether, the researchers note that additional, well-designed studies and trials are necessary before any firm conclusions can be drawn about its efficacy. The paper is accompanied by a second from researchers at the University of Cambridge analyzing relationships between vitamin D levels and the risk of mortality from several causes, as well as an editorial declaring that, despite much study, vitamin D is “no magic bullet.”

Previously: The Lancet documents waste in research, proposes solutions, “US effect” leads to publication of biased research, says Stanford’s John Ioannidis and Shaky evidence moves animal studies to humans, according to Stanford-led study
Photo by Colin Carmichael

Clinical Trials, Mental Health, Research, Stanford News

Examining an app’s effectiveness at helping those with PTSD

Examining an app's effectiveness at helping those with PTSD

Can a mobile app help people manage the symptoms of post-traumatic stress disorder? As some local readers may have heard on KCBS today (or may remember from a previous Scope entry), this is a question that a group of researchers here are studying.

I explain more about the app in a recent release:

The study involves the use of a Veterans Affairs-developed app designed to provide immediate help for patients’ symptoms. The app contains four sections: “learn,” which provides basic information about PTSD; “find support,” which helps users find professional care; “self-assessment,” which allows users to fill out a survey that measures PTSD symptoms; and “manage symptoms,” which provides tools to address acute symptoms such as insomnia and anger.

The VA-funded trial follows earlier research showing that the decrease in PTSD symptoms for those study participants who used the app for one month was significant when compared to participants in the control group who didn’t use the app. For this study, participants will use the app for three months and fill out online surveys at the start of the study and at the three-month follow-up.

The researchers are looking for 30 participants experiencing symptoms of PTSD; they must not be currently receiving care for the disorder and they must have either an iPhone or Android smartphone on which they can download the app being tested. Those interested in participating or learning more should contact study coordinator Nitya Kanuri at nkanuri@stanford.edu.

Previously: The remarkable impact of yoga breathing for trauma, Relieving stress, anxiety and PTSD with emerging technologies, Using a mobile-based app to help manage PTSD and Stanford and other medical schools to increase training and research for PTSD, combat injuries

Clinical Trials, Dermatology, Pediatrics, Research, Stanford News

Using Viagra to treat a rare childhood deformity: A research update

Using Viagra to treat a rare childhood deformity: A research update

Researchers at Lucile Packard Children’s Hospital Stanford are investigating a surprising treatment for a rare and potentially dangerous childhood deformity. As I’ve described previously, pediatric dermatologist Al Lane, MD, and his colleagues are studying the drug sildenafil – better known by its trade name, Viagra – as a treatment for lymphangioma. The condition, an overgrowth of the body’s lymph vessels, can cause disfigurement and even threaten children’s lives if the deformity impinges on essential body structures such as the airway.

“It can be lethal in 10 percent of people or more, and the problem is, we don’t know what’s the best treatment,” Lane told me.

Other treatments, such as surgery and sclerotherapy, are less effective than doctors would like: Afterward, the deformity often grows back.

A new publication from Lane’s team appeared this week in the Journal of the American Academy of Dermatology, reporting on the first seven patients to have their lymphangiomas treated with sildenafil. Though the idea of giving this drug to children might seem startling, it has a good safety profile and is already used in kids who have a form of high blood pressure in the lungs called pulmonary arterial hypertension. Lane realized that the medication might work for both PAH and lymphangioma when he treated a child with both conditions who was receiving the drug.

The new study shows mixed results. Six of the seven children responded to the medication, though not all responses were equally strong. One child’s deformity became worse while taking the drug. The team is now planning a larger, placebo-controlled, blinded study to investigate why they saw these differences.

“If we can identify which patients respond to sildenafil, we may get a better idea for the molecular mechanism of how it helps, and that could help us understand the disease more,” Lane said.

His team has applied for an orphan disease grant through the National Institutes of Health and the U.S. Food and Drug Administration and will find out in the fall if they’ve been funded.

Previously: Viagra may treat rare childhood deformity

Clinical Trials, Global Health, Infectious Disease, Pediatrics, Stanford News

Life-saving dollar-a-dose rotavirus vaccine attains clinical success in advanced India trial

Life-saving dollar-a-dose rotavirus vaccine attains clinical success in advanced India trial

dollar bill 2Nearly every child in the world has been infected with rotavirus at least once by the age of five. But kids in poor countries get the worst of it. Rotavirus mortality is low in the developed world, but in low-income countries it’s a killer, accounting for 85 percent of the estimated 180,000 to 400,000 annual deaths caused by the pathogen.

The disparity exists for at least two reasons.

First, widespread malnutrition results in a different epidemiology. For example, 70 percent of rotavirus hospitalizations in India happen the first year of life, compared with 40 percent in high- and middle-income countries.

Second, price. Vaccination is second only to gaining access to potable water as a low-cost, high-payoff  strategy for ensuring children’s health. But many vaccines are far too pricey for families living on incomes in the neighborhood of $1,500 per year. As a result, most childhood deaths from vaccine-preventable diseases happen in low-income countries. India has the most rotavirus deaths in the world, estimated at about 75,000-122,000 per year (close to a quarter of the worldwide total.)

So it’s great news that a new rotavirus vaccine developed by Indians for Indians has leaped the safety and efficacy thresholds of a late-stage clinical trial, in which more than 6,500 Indian infants were inoculated, and will likely become available in that country for less than a dollar a dose. (The full immunization procedure requires three separate doses.)

The results appear in a study just published in The Lancet and co-authored by a team including veteran rotavirus-vaccine developer Harry Greenberg, MD. An accompanying perspective piece co-written by Greenberg, who also directs the Stanford Center for Clinical and Translational Research and Education, states:

[P]roof of the efficacy of the… vaccine against a disease that affects almost every child in India, leads to millions of clinic visits and hundreds of thousands of hospital admissions, and kills roughly one child in every 175-200 born in India before their fifth birthday is cause for celebration.

The new vaccine was the first to be fully tested for efficacy in a randomized, double-blind, placebo-controlled clinical trial in India. Interestingly, its development began with the discovery, by an Indian pediatrician, that newborns were getting rotavirus infections in the hospital but not getting sick. The strain they were infected with turned out to be an attenuated mutant virus that turns on the body’s immune response without causing symptoms: in short, the ideal vaccine candidate.

Ultimately spearheaded by a young Indian biotechnology company, Bharat Biotech, the effort to capitalize on this promising episode of serendipity drew financial support from the Bill & Melinda Gates Foundation and technical assistance from the Government of India’s Department of Biotechnology, the United States’ Centers for Disease Control and Prevention, and Stanford, among others.  This international team of collaborators then spent more than 15 years turning the promise into a reality.

Previously: Trials, and tribulations, of a rotavirus vaccine
Photo by David Guo

Clinical Trials, Imaging, Neuroscience, Research, Stanford News, Women's Health

Estradiol – but not Premarin – prevents neurodegeneration in women at heightened dementia risk

Estradiol - but not Premarin - prevents neurodegeneration in women at heightened dementia risk

bottle of pillsWomen near the age of menopause and at elevated risk for dementia – owing, say, to a family history of Alzheimer’s disease, a personal history of major depression, or a genotype positive for the infamous Alzheimer’s-predisposing gene variant, ApoE4 – may want to consider talking to their doctor about estrogen-based hormone therapy.

In a brain-imaging study just published in PLOS ONE, hormone therapy protected key “early warning” brain regions from metabolic decline in women who fit that description – but only if they started therapy shortly after reaching menopause, and only if the pill they took contained just estradiol, the dominant female sex-steroid hormone. Premarin, a more widely used hormone-therapy formulation derived from the urine of pregnant mares, was far less protective.

Premarin contains more than 30 substances, with estradiol accounting for only about 17 percent. Other components exert various endocrinological effects on different tissues. In my release on the new study, I wrote:

More than 20 million women in the United States are between 45 and 55 years old – an age range at which many once were considered prime candidates for Premarin. Hormone therapy… was… widely heralded as protecting postmenopausal women from heart disease, osteoporosis and even cognitive decline.

Indeed, from 1992 through 2001 Premarin was the most widely prescribed drug in the United States. Then came the deluge. Here’s the backstory:

In July 2002, a large multicenter study of hormone therapy’s effects was abruptly halted when – contrary to expectations – woman assigned to PremPro (Premarin plus progestin, a synthetic version of progesterone, another important female steroid hormone) developed more cardiovascular disease than those getting a placebo. Within 18 months, about half of American women who’d been on hormone therapy abandoned it. Its use has since plunged considerably further.

Then in 2003, an ancillary study called WHIMS (“Women’s Health Initiative Memory Study”) reported that dementia incidence among 65- to 79-year-old women randomly assigned to PremPro was double  that of women on placebo. This disappointing finding was widely covered in the media.

But Rasgon and her colleagues’ findings are consistent with other analyses indicating that women initiating hormone therapy within five years of their last menstrual cycle experienced beneficial brain effects. In fact, major differences in trial design may explain the discrepancy between WHIMS’s decidedly negative results and the new study’s more nuanced ones.

The WHIMS women were older, on average, than those in Rasgon’s study and were beginning hormone therapy after a long hiatus during which their bodies were no longer producing substantial quantities of estrodiol. Moreover, the PremPro given to women in the active arms of WHIMS contained progestin – which, the new study shows, speeds metabolic deterioration in at least dementia-prone women’s brains.

Natalie Rasgon, MD, PhD, director of the Stanford Center for Neuroscience in Women’s Health and the study’s lead author, puts it plainly. “Hormone therapy’s neurological effect on women at risk for dementia depends critically on when they begin therapy and on whether they use estradiol or Premarin.”

Previously: Hormone therapy halts accelerated biological aging seen in women with Alzheimer’s genetic risk factor, Hormone therapy soon after menopause onset may reduce Alzheimer’s risk and Study shows common genetic risk factor for Alzheimer’s disrupts brain function in healthy older women, but not men
Photo by Canned Muffins

Clinical Trials, Immunology, Pediatrics, Research, Stanford News

Simultaneous treatment for several food allergies passes safety hurdle, Stanford team shows

Simultaneous treatment for several food allergies passes safety hurdle, Stanford team shows

milk and eggsLiving with one food allergy is a challenge; living with more than one can make ordinary activities such as eating at a restaurant feel downright impossible.

That’s because the standard medical advice for the 4 million Americans with food allergies is to avoid all of your allergy triggers, all the time – and, by the way, make sure you always carry injectable epinephrine in case you accidentally eat something contaminated with a food that triggers anaphylactic shock.

So it will be welcome news to these food-allergy sufferers to hear that a Stanford team is making progress on a new way to help them. In research published today in the journal Allergy, Asthma & Clinical Immunology, a team led by Kari Nadeau, MD, PhD, found that an experimental treatment already being widely tested for single food allergies, called oral immunotherapy, could be modified so that patients can be desensitized to multiple food allergens at the same time. The results now being reported are the products of a pair of phase-1 safety trials.

In our press release about the findings, Nadeau explained why she wanted to develop the new therapy:

“Parents came up to me and said things like, ‘It’s great that you’re desensitizing children to their peanut or milk allergies, but my daughter is allergic to wheat, cashews, eggs and almonds. What can you do about that?’” said Kari Nadeau, MD, PhD, associate professor of pediatrics at the medical school and an immunologist at Stanford Hospital & Clinics and Lucile Packard Children’s Hospital Stanford. Nadeau is the senior author of the new study.

… [O]ral immunotherapy is still experimental and quite slow: In prior studies, patients took as long as three years to become desensitized to one food. Being desensitized to several foods, one at a time, could prospectively take decades. Yet Stanford researchers succeeded in safely desensitizing patients to several food allergens at once and were able to speed up desensitization by supplementing oral immunotherapy with injections of omalizumab (brand name Xolair).

With omalizumab, patients were desensitized to up to five of their allergens in a median of 18 weeks; without the medication, the same process took a median of 85 weeks, the research team found. The published results add weight to the anecdotal findings from three of Nadeau’s patients who participated in the trial and shared their experience in a story in the New York Times magazine last spring.

The researchers stress that the treatment is still experimental and must be performed in a hospital setting, but they are excited by the next step in the process: a phase-2 trial to evaluate the therapy more rigorously in a larger number of patients. The phase-2 trial will be conducted at Stanford, where recruitment of new patients has already begun, and at four other centers across the country, which will begin recruiting patients in the coming months. Individuals who are interested in learning more about participating in the new studies can check the federal clinical trials website for opportunities in their region.

Previously: Researchers show how DNA-based test could keep peanut allergy at bay, A mom’s perspective on a food allergy trial and Searching for a cure for pediatric food allergies
Photo by Logan Brumm Photography and Design

Clinical Trials, Genetics, In the News, Stanford News

Huntington’s therapy discovered at Stanford shows positive results in humans

Huntington's therapy discovered at Stanford shows positive results in humans

There are definite perks to sticking with the same job for several years. For me, it means the chance to see the progression of research findings I first wrote about in their infancy actually enter human testing. Last week Raptor Pharmaceuticals, based in Novato, Calif., reported positive results in a clinical trial of a possible treatment for Huntington’s disease called RP103. RP103 is a delayed-release cysteamine – a compound first identified in 2002 as a potential therapy in the Stanford laboratory of Lawrence Steinman, MD. As I wrote in my release at that time (courtesy of the way-back machine):

By enhancing the brain’s natural protective response to the disease, researchers were able to alleviate the uncontrollable tremors and prolong the lives of mice with a neurological disorder that mimics Huntington’s. Their finding suggests that a similar treatment strategy may be effective in humans.

Raptor (a company which Steinman advises and in which he holds stock options) enrolled 96 patients in an 18-month-long double blind trial pitting RP103 against a placebo, followed by an 18-month period in which all the participants would receive RP103. Eighty-nine patients completed the first 18-month period; those who received the drug appeared to show slower progression in their disease than those who received the placebo.

It will likely still be years before we know whether the potential treatment will clear the necessary hurdles and become clinically available. But as Steinman said to me in a e-mail last week, “It’s very exciting to see this moving forward in humans.”

Previously: Drug found effective in two mouse models of Huntington’s disease, Amyloid, schmamyloid: Stanford MS expert finds dreaded proteins may not be all bad and Potential therapeutic target for Huntington’s disease discovered by researchers in Taiwan, Stanford

Clinical Trials, Fertility, NIH, Research, Women's Health

Testosterone therapy not effective for primary ovarian insufficiency-related depression, study finds

Testosterone therapy not effective for primary ovarian insufficiency-related depression, study finds

Primary ovarian insufficiency (POI), a condition affecting approximately 1 percent of women and teenage girls in the U.S., is characterized by ovaries that stop functioning normally before a woman is 40. POI may be a cause for irregular periods, reduced fertility, or health problems such as osteoporosis, and women with POI may also be at risk for depression and decreased quality of life. Treatments for POI may include hormone replacement therapy to restore estrogen and progesterone levels.

A recent study from the National Institutes of Health Clinical Center has examined the effect in women with POI of one year of hormone treatment that included testosterone.

From a release:

In the randomized, double-blind, placebo controlled study, 61 women used placebo patches and 67 women used patches that delivered 150 micrograms of testosterone a day, similar to the Intrinsa patch that was rejected by FDA as a treatment for low sexual desire in women.

After 12 months, testosterone levels were back up to normal for the women who got the treatment. The investigators saw no detrimental effects of testosterone, but they found no significant improvement either in measurements of quality of life, self esteem and mood compared with placebo.

Bringing testosterone back to normal doesn’t help these aspects of life, suggesting that it’s something other than testosterone that plays a role in mood problems for women with POI, concluded the researchers.

“This study makes an important contribution toward understanding what testosterone can and cannot do. With all the hype about testosterone and aging, it is important that the public have the facts,” NAMS Executive Director Margery Gass, MD, said in the release.

The study was published online in the journal Menopause.

Previously: An in-depth look at fertility and cancer survivorshipAsk Stanford Med: Expert in reproductive medicine responds to questions on infertility, Researchers describe procedure that induces egg growth in infertile women and Oh, baby! Infertile woman gives birth through Stanford-developed technique

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