Waiting for the Cure » trials

Nottingham Hookworm Results for Allergies and Asthma

admin — Wed, 20 Jan 2010 16:58:24 +0000

Disappointing. 10 hookworms didn’t really work statistically for asthma or allergies, but there were immune changes. I wonder what “mimic most closely natural infection” means (last line of abstract for asthma study)? Less at once, more often? Or more than 10? I am feeing extraordinarily lucky that 10 hookworms caused such a pronounced change in me; first for the worst, then for the better. I started with 10 hookworms De. 2007, got edema, arthritis, a fever, diarrhea. By month 4 I was in remission, but added 2-3 worms a week for a total of 37. Then I lost them somehow by September 2008 and lost efficacy.

I got 10 new hookworms in February 2009, then 10 more in late September 2009. My last egg count was 1400 epg. My CRP (measure of inflammation) has been normal since March 2009. So 20 worms are working for me. Weight’s been normal since March, I can eat most foods but still get diarrhea from too much fiber. Now my hormones are causing anxiety/depression, but I’m assuming that’s un-worm related. I’m almost 38 years old.

I wish we knew the ideal dosing number and dosing schedule. It seems that those with the best response are getting at least 20-30 hookworms, though I also know of Crohns patients who had to terminate because 20-25 worms were way too much at once. I wish these studies were faster since we’re just dosing in the dark.

The asthma study:

http://www.ncbi.nlm.nih.gov/pubmed/20030661

Experimental hookworm infection: a randomized placebo-controlled trial in asthma.

Feary JR, Venn AJ, Mortimer K, Brown AP, Hooi D, Falcone FH, Pritchard DI, Britton JR.

Division of Epidemiology and Public Health, University of Nottingham, Nottingham, UK.

Summary: Background Epidemiological studies suggest that hookworm infection protects against asthma, and therefore that hookworm infection may have a direct or an indirect therapeutic potential in this disease. We now report the first clinical trial of experimental hookworm infection in people with allergic asthma. Objectives :To determine the effects of experimental hookworm infection in asthma. Methods “Thirty-two individuals with asthma and measurable airway responsiveness to adenosine monophosphate (AMP) were randomized and double blinded to cutaneous administration of either ten Necator americanus larvae, or histamine solution (placebo), and followed for 16 weeks. The primary outcome was the change in provocation dose of inhaled AMP required to reduce forced expiratory volume in 1 s by 20% (PD(20)AMP) from baseline to week 16. Secondary outcomes included change in several measures of asthma control and allergen skin sensitivity and the occurrence of adverse effects. Results Mean PD(20)AMP improved in both groups, more in the hookworm [1.49 doubling doses (DD)] than the placebo group (0.98 DD), but the difference between groups was not significant (0.51 DD; 95% confidence interval: -1.79 to 2.80; P=0.65). There were no significant differences between the two groups for other measures of asthma control or allergen skin sensitization. Infection was generally well tolerated. Conclusions” Experimental infection with ten hookworm larvae in asthma did not result in significant improvement in bronchial responsiveness or other measures of asthma control in this study. However, infection was well tolerated and resulted in a non-significant improvement in airway responsiveness, indicating that further studies that mimic more closely natural infection are feasible and should be undertaken

And the allergy one:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2728895/?tool=pubmed

Clin Exp Allergy. 2009 Jul;39(7):1060-8. Epub 2009 Apr 20.

Safety of hookworm infection in individuals with measurable airway responsiveness: a randomized placebo-controlled feasibility study.

Feary J, Venn A, Brown A, Hooi D, Falcone FH, Mortimer K, Pritchard DI, Britton J.

Division of Epidemiology and Public Health, University of Nottingham, UK. johanna.feary@nottingham.ac.uk

BACKGROUND: Epidemiological evidence suggests that hookworm infection protects against asthma. However, for ethical and safety reasons, before testing this hypothesis in a clinical trial in asthma it is necessary to establish whether experimental hookworm infection might exacerbate airway responsiveness during larval lung migration. OBJECTIVE: To determine whether hookworm larval migration through the lungs increases airway responsiveness in allergic individuals with measurable airway responsiveness but not clinical asthma, and investigate the general tolerability of infection and effect on allergic symptoms. METHODS: Thirty individuals with allergic rhinoconjunctivitis and measurable airway responsiveness to adenosine monophosphate (AMP) but not clinically diagnosed asthma were randomized, double-blind to cutaneous administration of either 10 hookworm larvae or histamine placebo, and followed for 12 weeks. The primary outcome was the maximum fall from baseline in provocative dose of inhaled AMP required to reduce 1-s forced expiratory volume by 10% (PD(10)AMP) measured at any time over the 4 weeks after active or placebo infection. Secondary outcomes included peak flow variability in the 4 weeks after infection, rhinoconjunctivitis symptom severity and adverse effect diary scores over the 12-week study period, and change in allergen skin test responses between baseline and 12 weeks. RESULTS: Mean maximum change in PD(10)AMP from baseline was slightly but not significantly greater in the hookworm than the placebo group (-1.67 and -1.16 doubling doses; mean difference -0.51, 95% confidence interval -1.80 to 0.78, P=0.42). Symptom scores of potential adverse effects were more commonly reported in the hookworm group, but infection was generally well tolerated. There were no significant differences in peak-flow variability, rhinoconjunctivitis symptoms or skin test responses between groups. CONCLUSION: Hookworm infection did not cause clinically significant exacerbation of airway responsiveness and was well tolerated. Suitably powered trials are now indicated to determine the clinical effectiveness of hookworm infection in allergic rhinoconjunctivitis and asthma.

To the Medical Community, or Dear Dr. Weinstock

admin — Tue, 29 Sep 2009 16:20:31 +0000

Article after article extolling the virtues of helminths’ ability to prevent allergies and autoimmune diseases always end in quotes like this:

“The hope is that the work could aid the development of new treatments which work in the same way as gut parasites, by dampening down or rebalancing the immune system so that the body does not respond to allergens and trigger asthma attacks.”

“Here, the view is presented that assessment of the immunophysiological response to helminths could identify that infection with specific parasites would be therapeutically useful (although many helminths could not fulfil this role) and lead to precise knowledge of the immune events following infection, to identify ways to intervene in disease processes (in the absence of infection per se) that can be used to treat, and eventually cure, inflammatory and autoimmune disease.”

Dr. Joel Weinstock, one of the leaders in helminth therapy, criticizes operations like AIT for going ahead and giving out helminths before the research comes in:

“It is a legitimate field, but it’s been bootlegged,” said Dr. Joel Weinstock, a professor of medicine at Tufts University who’s studied parasitic treatment and is working to test the therapy. “The question is, what are you actually buying [from these companies]?”

Weinstock told ABC that selling parasites online “hurts the science, and when people do this it makes people skeptical.”

I would like these researchers to think about this deeply. How many years away is your medicine that mimics the worms’ effects? How accessible is the one helminth treatment that is sanctioned by Dr. Weinstock? How many trials are currently available that one can participate safely in helminth research?

I cannot answer the first question; my guess is at least a decade. Even 5 years is too long. The second question: TSO costs well over $10,000 a year for a therapeutic dose, and when I tried to get it in 2007, it was blocked importation by the FDA. For trials? There is currently 1; TSO for MS at the University of Minnesota. There will be another one at University of Nottingham for MS, but it’s not even recruiting. And that’s it. According to Weinstock, and most other researchers, we must wait until the overwhelming science proves that helminths do indeed dampen the inflammatory cascade that leads to the suffering caused by autoimmune diseases.

I have Crohn’s disease. I’ve had it for 21 years. I’ve already had 1/4 of my colon cut out and resectioned. I have a narrowed ileal-cecal valve that pains me often. I’ve failed every available medication on the IBD market; the only medicine I haven’t tried is Tysabri, with a 1 in 1000 chance of a fatal brain disorder. The risks of helminths are…anemia in large numbers. But you can control the numbers if you use hookworms, or whipworms. I suppose there is risk of coinfection, and a risk that the companies doling out helminths aren’t giving us what they say.

But I’ve seen hookworm eggs under my microscope and other patients have confirmed O&P’s for hookworm ova. Whipworms can be seen in a colonoscopy. My eosoniphils have risen after infection with hookworms, and I experienced all of the side effects that are usual for hookworms. I have taken blood tests to rule out the commonest co-infections. And a small dose of hookworms lowered my inflammation to 0, since I’ve been taking monthly blood tests before and after being infected. Do you need more proof?

If I waited for your molecule, let me describe my life. Emaciation, night sweats, eating a small handful of blended foods. Bedridden, unable to care for my children, in terrible pain, bowel blockages nightly, diarrhea so uncontrollable it spewed out on the floor as I ran to the bathroom every night. 10 + bowel movements a day. Depends for underwear, anemia, weakness, fever, and fatigue. Perhaps Tysabri would work, but after suffering near fatal neutropenia from 6MP, an allergic reaction to Humira, the fear of progressive multifocal leukoencephalopathy is strong. Would my children enjoy watching their mother die?

I understand the criticism. I understand the concern. I tried to get a helmith immunologist to study my effects from the hookworms at UCSF. I was willing to do before and after colonoscopies, monthly blood tests, tissue samples, to research the immunological effects of hookworms on my well-established Crohn’s. We were rejected by the ethics committee. What more can I do?

I’ve published this blog, been interviewed by CBS, have written to Dr. Prtichard and Dr. Weinstock, tried to spur the movement of connecting us experimenters with researchers, and have been rejected, time and time again. We are willing to do things in a controlled setting, but UCSF is not. I’ve asked for help with quantifiying egg counts, to no avail. My doctor says I am the expert in this therapy, which is a joke. There are immunologists who when interviewed, say this therapy has much merit. But go to your doctor and they will not sanction this. “It’s premature. You must wait for the research. Here, try Tysabri. I hope you don’t die.”

If you moved a little faster. If you had multiple trials for people to sign up and get a safe infection from a well-respected institution, then I wouldn’t balk so much. Study after study is pouring in, in the mouse model, in huge population studies, scientists are proving that the helminth is a key player in a well-orchestrated immune system.

Please don’t be so dismissive. We are suffering horribly. And you are taking far too long.

eosinophilia: significance?

Wed, 11 Feb 2009 14:56:40 +0000

There are very few studies on the effect of helminths on humans. As a patient trying this therapy, there are few immune markers we have on hand to check immune response. We have measures of inflammation, like CRP and SED rates, but only in the research setting can one measure IL-10, the T 1 and T2 arms, etc. All we have is eosinophilia and standard stool tests to assess worm burden.

Eosinophils rise in response to hookworm infection, seeming to peak between weeks 3-10. This study describes that eosiniphils peak between days 38-64 :

http://www.ajtmh.org/cgi/content/abstract/37/1/126

Peaks between weeks 3-9:

http://www.ajtmh.org/cgi/content/full/75/5/914#F5

Starts to be elevated at days 14-21, peaked on day 42 and declined to
a persistently elevated level:

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1809522

Peaked week 5, declined by week 20:
“In the CD cohort, blood eosinophilia developed from week 5 (mean
2.60×109/l (1.89) v week 1 0.18×109/l (0.10) v week 20 0.59 (0.20)). ”

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1856386

But my favorite study, the MS study in Argentina, where they tracked 12 MS patients already infected with helminths and compared them to 12 other MS patients over a 4.6 year period, only recruited the helminth infected patients if their eosinophelia was high, (800-1800 mm3) and it stayed that way for the duration of the study. Their quantitative egg counts were also high: between 1,180 and 9,340 eggs/gram.

Eosinophils reflect parasitic infection, and the higher the number, usually the larger the worm burden. One indication that one has lost their worm infection would be having an elevated EOS for an extended length of time, then having it fall to baseline. Obviously, stool tests would confirm this, as well as symptom regression. In the dose-ranging trial, the higher doses resulted in higher EOS counts, though they did not test longer than 12 weeks.

I only tested my EOS at baseline and 18 weeks, so I never tracked a rise and fall. Baseline values were 74 cells/mcL and only rose to 192 post infection. (Normal is 15-550). Remember, I added worms from weeks 10-18, which may have provoked an immune response that curtailed the new worms from attaching, and possibly displaced some of the first 10, like this capsule endoscopy study shows. So by week 18, perhaps I had very few worms…

I will be testing EOS at weeks 3, 6, 9, and 12 to see how they respond to 10 larvae. I don’t think 10 hookworms are going to be enough to cause persistent eosinophilia. And like the MS study, it seems important to get and maintain a large enough worm burden to stimulate eosinophilia, and maintain a higher egg count. I’m very curious what my results will be this time…

Nottingham’s Trial Notes

Fri, 23 Jan 2009 14:56:00 +0000

Just found the on-line protocol for the Crohn’s study at Nottingham University. For those of you with Crohn’s experimenting with hookworms, though most of the immune blood tests will be unavailable to us, it might be nice to follow some of the other protocol. The CRP and SED rate are taken at baseline, then at weeks 3, 6, 9, and 12. (They eradicate the hookworms at week 12, but follow up for another month.) Fecal egg counts are done at week 12. Of course, there’s also the CDAI, the Harvey Bradshaw Index (HBI), and quality of life IBD questionairre (IBDQ).

One of the frustrations I have in experimenting with this therapy, and of AIT, is the lack of diagnostic pursuit of patient’s effects. Most patients are not doing before and after screening, and often aren’t even communicating about their long-term effects from hookworms. Patient’s doses, frequency of doses, and clinical response are only known by AIT and none of the rest of us are able to access that data to learn from. I wish there was an anonymous database accessible online that would list the diseases, patient’s blood scores at baseline, side effects within the first 4 months, and when efficacy began, if it did. Although each person’s reaction to hookworm is different, the more we quantify and correlate our response, the more patterns might emerge that would help future patients. But alas, it’s not my business, so I am correlating what I find here, and when I redose in a few weeks, will try to take my own advice and do all I can to track my response to help future people wishing to experiment outside the trials.

Week 4: Nottingham Trials

Thu, 17 Jan 2008 12:47:00 +0000

I just got an email from Nottingham. Inviting me to be in their Crohn’s disease trial, though they realized that distance could be a problem. The English was so proper:

“Whilst we would be delighted to have you participate in our trial, the tyranny of distance seperates us.” I don’t think I’ve ever used the word “whilst”.

Oh, the comfort of being in a study; to be able to go to a doctor right now and have him know what he’s doing, knowledge of the treatment. Someone to give me comprehension and assurance, expertise! Especially if he spoke like Dr. Fortun. I would have at least felt well taken care of.

Instead, I’ve got the snarl of Dr. Terdiman. What else have I caught in Mexico? My UCSF post doc dropped me after visiting the ethics committee, who wouldn’t condone a Tijuana clinic without any proof of the safety or lack of pathogenicity of their worms. My local doctor thinks I’m brave and vaguely remembers reading some article on parasite proteins. I feel so alone.

No one but Dr. Pritchard really knows what’s happening to me. I emailed him to ask if he’s ever seen someone develop arthritis from a light hookworm infection. Never. I’m so fucking unique. Maybe there’s a pathogen that came from Jasper’s sample? I still haven’t seen the paperwork on the resevoir donors, so now I’ve got reactive arthritis, oedema, or whatever this is to add to the worry list that I’m just supposed to trust will go away.

I just wish I could stop having unusual reactions to things. Or when I do, have someone tell me exactly what went wrong. Not, “it may be an allergic reaction,” or “we don’t know what’s happening to you, possibly you have latent RA?” I just want to know what to expect sometimes. A longing for some pattern to cling to.

I chose 10 hookworms to minimize my symptoms but it hasn’t been minimal at all. At least I was wise not to get 50, but I just want someone to go to for reassurance when I wake up sore and tired.

I don’t know what to write back to Nottingham. Sorry, but I already found me some hookworms. Whilst I just payed the equivalent of your required 6 visits to England, I cannot afford to get the placebo. So I am all alone with 10 hookworms doing God knows what, with no support.

I want to sit down in an office with an expert. Who actually knows volumes more than me and can fit me in the larger puzzle of decades of experience. Who’s written papers on Pub Med. If I could only travel to Nottingham with my worms already in me, have them take a blood test and explain to me everything I’m going through. Tell me what the next few months will bring, and what precautions I should take. No mysteries. No bizarre symptoms. Everything previously studied and predictable…

“Oh yes, this can happen. It should go away by week X… Whilst it can be unusual, some people’s allergic response can manifest in this manner…” My lovely English dreams.

Instead I’m here, in this small town. With a forum of novices, no doctor who understands what I’m doing, and no expert to tell me I’ll be OK. How I wish I went to Nottingham. Perhaps one day.

Day 1: No Itch

Wed, 19 Dec 2007 16:00:30 +0000

I am back at my sister’s house and my two girls stand around my bandage as I slowly unroll the gauze to examine my rash. I never felt an itch. After the initial larvae burrowing through my skin, I’ve felt nothing but the tightness of the bandage. I guess 10 larvae does cause little reaction, like the first Nottingham dosing trial found. I hope I get something though, so I know they’re still alive. All I see is the folds of skin from the tight bandage, and one single, tiny red dot. I wonder if all 10 entered in the same place? I know they’re microscopic, these larvae (thank God), but I expected multiple entry points, an indescribable itch. This is anticlimatic. A little dot?

Oh well, I shouldn’t complain. Hopefully it means my reaction to them will be muted, if anything. My girls are more impressed by the bandage, and busy themselves wrapping it around their ankles.

We rest in the morning, pack the car, and ready ourselves for our journey north. It is almost Christmas. Hookworm larvae are swimming in my blood stream. I’ve had my very expensive, exotic vacation. Now we can go home.