Clinical trials of helminthic therapy

    From Helminthic Therapy wiki

    This page, which is still under construction, aims to explain the ins and outs of clinical trials of helminth therapy, listing both those trials that have already been carried out and those that would be interesting to perform.

    Clinical trials by disease[edit | edit source]

    Allergic rhinitis[edit | edit source]

    Asthma[edit | edit source]

    Autism[edit | edit source]

    • 2014-2015 - TSO - 0522-12-HMO - Jerusalem, Israel - TSO in Pediatric Autistic Spectrum Disorders (TSO). Treatment: T. suis 2500 or 7500 ova or placebo orally every 2 wks for 16 wks. Results: study terminated due to lack of available study agent

    Coeliac / celiac disease[edit | edit source]

    Crohn's disease[edit | edit source]

    Diabete type 2[edit | edit source]

    Food Allergies[edit | edit source]

    • 2010-2011 - TSO - Phase 1 - 2009P000414 - Boston (USA) - Trichuris Suis Ova Therapy for Mild to Moderate Peanut and Tree Nut Allergy in Adults and Children

    Multiple sclerosis[edit | edit source]

    • 2012-2017 - TSO - Phase 2 - TRIOMS - Berlin La Charité - Trichuris Suis Ova (TSO) in Recurrent Remittent Multiple Sclerosis and Clinically Isolated Syndrome (TRIOMS) - study protocol. Treatment : Oral inoculation (2,500 ova) every 2 weeks for 12 months. Placebo group included. Total study (n = 50) Results:
    • 2011-2016 - NA - WIRMS - University of Nottingham - Worms for Immune Regulation of Multiple Sclerosis (WIRMS). Treatment: Single dermal inoculation (25 larvae) at week 0 (n = 36). Placebo group included. Results: 2020 Jun 15 Hookworm Treatment for Relapsing Multiple Sclerosis -- Full text (While the primary statistical endpoint of this trial - the cumulative number of new/enlarging T2 and new enhancing T1 lesions at month 9 - was not significantly different between the hookworm group (154) and the placebo group (164), a closer examination of the data reveals that more than half the patients given hookworms did not have any new lesions. “The findings of the research… show that infecting MS patients with a safe dose of… Necator americanus induces immunoregulatory responses and boosts the number of cells which help keep the immune system under control.” [3] The trial’s lead researcher concluded, “I think there would be a niche for this approach - for individuals with mild disease who don't want to take immunomodulating drugs for life and would prefer a more natural approach.” [4])
    • 2011 Apr - The impact of parasite infections on the course of multiple sclerosis. Treatment: Prospective clinical monitoring study of parasite-infected patients with relapsing-remitting disease (n = 12). Four patients received anti-parasitic treatment over the monitoring period. Results: After antiparasitic treatment, patients presented with increased numbers of exacerbations. This was met with a decrease in IL-10- and TGFβ-secreting cells
    • 2008 - NA - WIRMS-1 - University of Nottingham - Immunoregulation by Controlled Parasite Exposure in Multiple Sclerosis. (WIRMS-1). Treatment: Single dermal inoculation (25 larvae) at week 0. Placebo group included. Results: Withdrawn prior to enrollment, superceded by similar study
    • 2007 Feb - Association between parasite infection and immune responses in multiple sclerosis -- PDF (Also reported by Science Daily [5] and the BBC. [6]) This was the first study to explore the effect of helminth infection on immune response and the natural course of Relapsing Remitting Multiple Sclerosis. It showed that MS progressed much more slowly in patients who hosted intestinal worms. Treatment: Prospective clinical monitoring study of parasite-infected patients (n = 12) and non-infected patients (n = 12). Results: Parasite-infected patients presented with fewer numbers of exacerbations. A significant increase in IL-10 and TGFβ and a decrease in IL-12 and IFNγ observed in self-reactive cells

    Psoriasis[edit | edit source]

    Comments from William Parker : 2017 Jul 15 Not infection with parasitic worms, but rather colonization with therapeutic helminths | PDF "The report by Williams and colleagues in the August issue of Immunology Letters describes a case in which a scientist exposed himself/herself to a helminth well-known among the veterinary community, the porcine whipworm. The intention was to observe the effects of exposure to the helminth on the scientist’s immune disorder and to monitor the fate of the organisms following that exposure. The scientist saw improvement in his or her psoriasis (...) Fortunately, Williams used a lower pH formulation (produced in-house using the ParaTech protocol and stored at pH 1"

    Rheumatoid arthritis[edit | edit source]

    • 2011 - TSO - TSORA. Immanuel Krankenhouse in Berlin. Trichuris suis ova (TSO) as a additional therapy for rheumatoid arthritis patients with insufficient response to methotrexate. A prospective, double-blind, randomized, controlled monocenter study. Treatment: Oral inoculation (2,500 ova) every 2 weeks for 24 weeks. Placebo group included. Total study (n = 50). Results : "Prematurely Ended"

    Ulcerative colitis[edit | edit source]

    • 2012-2015 - TSO - MUCUS - NYU Langone Health (USA) - Mucosal Immunity of Ulcerative Colitis Patients Undergoing Therapy With Trichuris Suis Ova - Treatment: Two arms. First arm, oral inoculation (2,500 ova) at 2-week intervals for 12 weeks followed by placebo for 12 weeks. Second arm, placebo for 12 weeks followed by oral inoculation (2,500 ova) at 2-weeks intervals for 12 weeks. Results: No study results posted

    Well people[edit | edit source]

    • 2024-2026 - NA - HiBiSki - Leiden (NLD) - Investigating the Local Immune Responses in the Skin After Repeated Hookworm Infection
    • 2015-2026 - NA - SVI-CH-01 - Leiden (NLD) - An Experimental Infection Study of Dermally-applied Infectious Necator Americanus Hookworm Larvae in Hookworm-naïve Adults
    • 2018-2019 - NA ITCHHI - Leiden (NLD) - Immunisation, Treatment and Controlled Human Hookworm Infection
    • 2012-2012 - TSO - NCT03079700 - Denmark - Mucosal and Systemic Immune Modulation From Trichuris Suis in a Self-infected Individual. "The included volunteer is a researcher within parasitology with main focus on Trichuris trichiura and Trichiura suis. He planned to infect himself and contacted our department with the purpose of being monitored during this infection for safety (medical supervision) and research reasons. The only clinical criterion for his inclusion in the study was that he was healthy."

    Defective clinical trials[edit | edit source]

    Coronado Biosciences (Fortress Biotech) / Dr. Falk Pharma GmbH clinical trials[edit | edit source]

    For details of some of the issues with these trials, see: Problems with clinical trials using live helminths.

    See Press Release for more details.

    Comments from William Parker : 2017 Jul 15 Not infection with parasitic worms, but rather colonization with therapeutic helminths | PDF. "the field suffered more than a catastrophic failure when Ovamed, the owner of the TSO technology, shut down clinical trials in mid-2015 due to a lack of effectiveness. But failure of a helminth in a clinical trial, more so than failure of a precisely characterized pharmaceutical, is not necessarily a sign that potential is low. Our socio-medical studies (2) suggest that storage of TSO at a pH above 4, the standard used in the Ovamed-sponsored trials, may impede the therapeutic effect of the organisms in humans". Fortunately, Williams used a lower pH formulation (produced in-house using the ParaTech protocol and stored at pH 1; personal communication from coauthor Nejsum to William Parker), consistent with the formulation that worked in early trials and that received consistently high marks from individuals self-treating with helminths (2). Importantly, the Williams et al study highlights the fact that it is premature to put nails in the coffin of therapeutic TSO."

    Autism

    • 2014-2015 - CNDO 201-101 - Efficacy and Safety of Trichuris Suis Ova (TSO) as Compared to Placebo in Autism Spectrum Disorder. Treatment: T. suis 2500 ova or placebo orally every 2 wks for 4 wks followed by 7500 ova every 2 wks for 12 wks, 4-week washout, then crossover. Results: Study terminated prior to enrollment.

    Crohn's disease

    • 2010-2014 - TSO - Phase 2 - TRUST-2 - Trichuris Suis Ova (TSO) Suspension Versus Placebo in Active Crohn's Disease (TRUST-2). Treatment: Oral inoculation (low, medium, and high-dose ova) with placebo group included. Results: study results unknown
    • 2012-2014 - TSO - Phase 2 - TRUST-I Phase 2 : Efficacy and Safety of Trichuris Suis Ova (TSO) as Compared to Placebo (TRUST-I). Treatment: Oral inoculation (7,500 ova) at 2-week intervals for 10 weeks. Placebo group included. Results: "In the overall patient population, response rate of patients on TSO did not separate from that of placebo" [8]. "The company later canceled a European Phase 2 study due to lack of efficacy, the London School of Hygiene and Tropical Medicine's Helmby wrote in BMC Immunology" [9]
    • 2011-2012 - TSO - Phase 1 - CNDO 201-002 - A Sequential Dose-Escalation, Double-Blind, Placebo-Controlled, Phase I Study to Evaluate the Safety and Tolerability of Single Doses of 3 Different Doses of Oral CNDO 201 Trichuris Suis Ova Suspension (Tso) in Patients With Crohn's Disease. Treatment: Sequential dose escalation (500, 2,500, and 7,500 ova) given orally (n = 27). Placebo group included (n = 9). Results: Minor adverse events seen in both placebo and treatment groups. Infection resulted in no obvious benefit to pathology. Seven thousand five hundred ova dose was safe and well tolerated

    Relapsing-remitting multiple sclerosis

    Psoriasis

    • 2014-2015 - CNDO 201-201 - TSO for Plaque Psoriasis. Treatment: Three arms. First arm, oral inoculation (7,500 ova) every 2 weeks for 10 weeks. Second arm, oral inoculation (15,000 ova) every 2 weeks for 10 weeks. Third arm, placebo comparator. Results: Withdrawn
    • 2013-2014 - TSOPSO13 - Tufts (USA) - Efficacy Study of Trichuris Suis Ova to Treat Chronic Plaque Psoriasis. Treatment: Oral inoculation (7,500 ova) every 2 weeks for 14 weeks. Results: Lack of efficacy
    • 2013-2014 - GCO 12-188 - Mount Sinai (USA) - Safety and Effectiveness of CNDO 201Trichuris Suis Ova (TSO) for the Treatment of Moderate to Severe Plaque Psoriasis. Treatment: Two arms. First arm, oral inoculation (2,500 ova) every 2 weeks for 10 weeks. Second arm, oral inoculation (7,500 ova) every 2 week for 10 weeks. Total study (n = 8). Resuts: Study results unknown

    Ulcerative Colitis

    • 2013-2015 - TSO - CNDO 201 - A Prospective, Randomized, Double-blind, Placebo-controlled Phase II Clinical Study of Trichuris Suis Ova Treatment in Left-sided Ulcerative Colitis and Its Effects on Mucosal Immune State and Microbiota

    ParaTech A/S[edit | edit source]

    ParaTech is a danish company that produce TSO.

    Ulcerative Colitis

    NB. Subjects in the treatment arm of this trial received a dose of 7,500 TSO every second week for 24 weeks. This was a significant deviation from the much lower level of dosing that had been established empirically by the Tufts Medical Center team involved in the early clinical trials of TSO [12] [13] [14] [15] and which had been further confirmed as the optimal level for dosing with this organism during more than a decade of use by thousands of customers of Ovamed, who marketed the product from 2003 onwards, and, later, Tanawisa.
    This collective experience had shown that a course of 10 fortnightly doses of 2,500 TSO would frequently produce disease remission in ulcerative colitis and that, if remission were not achieved by this means, a further course of 10 fortnightly doses of 2,500 TSO would often prove to be effective. Only in the few cases where this second course of treatment has failed to produce complete remission, is there any need to escalate the dosage, first to 5,000 TSO every two weeks, and then, if necessary, to 7,500 TSO fortnightly.
    Starting with 7,500 ova at the outset of treatment, as was done in the PROCTO trial, is not only inadvisable on the grounds of cost, but also pointless from the therapeutic perspective. Moreover, it is possible that commencing with this unnecessarily excessive dose may trigger a more aggressive immune response by the host to the TSO product, which might result in a greater loss of organisms than would have been the case with a lower dose, potentially resulting in a reduction in therapeutic effect.
    There is also uncertainly about the pH of the solution used to store the TSO product used in this trial since there is no mention of the formulation’s details in the published paper. If a pH any higher than the 2.4 that was used successfully in the early Tuft’s trials was employed in this later study, this would cast further doubt on the reliability of the conclusions drawn by its authors. (See: Problems with clinical trials using live helminths.) The study's supervising author has been approached for clarification on the product's pH.

    The reintroduction to the digestive tract of a controlled number of specially domesticated, mutualistic helminths (intestinal worms) in the form of microscopic eggs or larvae to reconstitute a depleted biome to treat or prevent chronic inflammation, autoimmune disease and other immune-related disorders, including allergy.

    A helminth that lives in the small intestine. Necator americanus (NA) is the only hookworm species used in helminthic therapy. Its microscopic larvae are applied periodically to the skin.

    a change which is a result or consequence of an action or other cause.

    the human hookworm, Necator americanus

    the ova (eggs) of the porcine (pig) whipworm, Trichuris suis

    A helminth that lives in the small intestine. Necator americanus (NA) is the only hookworm species used in helminthic therapy. Its microscopic larvae are applied periodically to the skin.

    The introduction of an infectious agent into an organism. Helminth inoculation

    Also known as regional enteritis, this is an inflammatory disease of the intestines that may affect any part of the gastrointestinal tract from mouth to anus, causing a wide variety of symptoms. It primarily causes abdominal pain, diarrhea (which may be bloody if inflammation is severe), vomiting or weight loss, but may also cause complications outside the gastrointestinal tract such as skin rashes, arthritis, inflammation of the eye, tiredness and lack of concentration.

    A helminth that lives in the small intestine. Necator americanus (NA) is the only hookworm species used in helminthic therapy. Its microscopic larvae are applied periodically to the skin.

    Inflammatory bowel disease is a group of conditions affecting the gastrointestinal (GI) tract, particularly the colon and small intestine. The major types of IBD are Crohn's disease and ulcerative colitis (UC).

    A helminth with a tapering whiplike body that lives in the colon. In helminthic therapy, the microscopic eggs of either the human Trichuris trichiura (TTO) or pig Trichuris suis (TSO) are taken in a drink.

    Ulcerative colitis (Colitis ulcerosa, UC) is a form of inflammatory bowel disease (IBD) which specifically affects the large intestine, or colon, causing characteristic ulcers, or open sores. The main symptom of active disease is constant diarrhea mixed with blood, of gradual onset.

    The active immature form of an insect, or an animal such as a helminth, which develops from an egg and eventually transforms again into its adult state.

    Multiple sclerosis (also known as disseminated sclerosis) is a chronic, typically progressive disease involving damage to the sheaths of nerve cells in the brain and spinal cord, whose symptoms may include numbness, impairment of speech and of muscular coordination, blurred vision and severe fatigue.

    The species of human hookworm used in helminthic therapy. Its microscopic larvae are applied periodically to the skin.

    An organism that lives in or on another organism (its host) and benefits at the host’s expense. (The organisms used in helminthic therapy are, strictly speaking, not parasites, but mutualists, because they have a mutually beneficial symbiotic relationship with their hosts.)

    An organism that lives in or on another organism (its host) and benefits at the host’s expense. (The organisms used in helminthic therapy are, strictly speaking, not parasites, but mutualists, because they have a mutually beneficial symbiotic relationship with their hosts.)

    An organism that lives in or on another organism (its host) and benefits at the host’s expense. (The organisms used in helminthic therapy are, strictly speaking, not parasites, but mutualists, because they have a mutually beneficial symbiotic relationship with their hosts.)

    An intestinal worm which grows large enough to be seen with the naked eye when mature but which is microscopic when administered in helminthic therapy. Wikipedia:Helminths

    The porcine (pig) whipworm used in helminthic therapy and taken as microscopic eggs (TSO) in a drink every two weeks.

    Ulcerative colitis (Colitis ulcerosa, UC) is a form of inflammatory bowel disease (IBD) which specifically affects the large intestine, or colon, causing characteristic ulcers, or open sores. The main symptom of active disease is constant diarrhea mixed with blood, of gradual onset.

    The human whipworm used in helminthic therapy and taken periodically as microscopic eggs (TTO) in a drink.

    the degree to which something is successful in producing a desired result; success.

    An intestinal worm which grows large enough to be seen with the naked eye when mature but which is microscopic when administered in helminthic therapy. Wikipedia:Helminths

    the ability to produce a desired or intended result.

    An intestinal worm which grows large enough to be seen with the naked eye when mature but which is microscopic when administered in helminthic therapy. Wikipedia:Helminths

    Helminth-Induced Immunomodulation Therapy. This term was adopted by researchers investigating the effects of TSO in patients with MS. [16]

    Microorganisms that are believed to provide health benefits when consumed.

    Ulcerative colitis (Colitis ulcerosa, UC) is a form of inflammatory bowel disease (IBD) which specifically affects the large intestine, or colon, causing characteristic ulcers, or open sores. The main symptom of active disease is constant diarrhea mixed with blood, of gradual onset.

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