Controlled Hookworm Infection for Medication-free Maintenance in Patients with Ulcerative Colitis: A Pilot, Double-blind, Randomized Control Trial

Abstract

Background Human hookworm has been proposed as a treatment for ulcerative colitis (UC). This pilot study assessed the feasibility of a full-scale randomized control trial examining hookworm to maintain clinical remission in patients with UC. Methods Twenty patients with UC in disease remission (Simple Clinical Colitis Activity Index [SCCAI] ≤4 and fecal calprotectin (fCal) <100 ug/g) and only on 5-aminosalicylate received 30 hookworm larvae or placebo. Participants stopped 5-aminosalicylate after 12 weeks. Participants were monitored for up to 52 weeks and exited the study if they had a UC flare (SCCAI ≥5 and fCal ≥200 µg/g). The primary outcome was difference in rates of clinical remission at week 52. Differences were assessed for quality of life (QoL) and feasibility aspects including recruitment, safety, effectiveness of blinding, and viability of the hookworm infection. Results At 52 weeks, 4 of 10 (40%) participants in the hookworm group and 5 of 10 (50%) participants in the placebo group had maintained clinical remission (odds ratio, 0.67; 95% CI, 0.11-3.92). Median time to flare in the hookworm group was 231 days (interquartile range [IQR], 98-365) and 259 days for placebo (IQR, 132-365). Blinding was quite successful in the placebo group (Bang’s blinding index 0.22; 95% CI, −0.21 to 1) but less successful in the hookworm group (0.70; 95% CI, 0.37-1.0). Almost all participants in the hookworm group had detectable eggs in their faeces (90%; 95% CI, 0.60-0.98), and all participants in this group developed eosinophilia (peak eosinophilia 4.35 × 10^9/L; IQR, 2.80-6.68). Adverse events experienced were generally mild, and there was no significant difference in QoL. Conclusions A full-scale randomized control trial examining hookworm therapy as a maintenance treatment in patients with UC appears feasible.

Helminths' therapeutic potential to treat intestinal barrier dysfunction

“…It has the potential to protect the host from a range of allergic, inflammatory, autoimmune and metabolic diseases; it is considered by many as a 'natural' alternative to conventional therapies; helminths are safe and generally well-tolerated when given as a controlled dose; and N. americanus resides in the body for several years, meaning a single dose could potentially deliver a prolonged benefit without the need for repeat dosing. 8,[13][14][15] These significant clinical advantages have been the driving force behind continued efforts by clinicians and researchers to investigate helminth therapy and the mechanism of action.…”

“…Human clinical trials using controlled doses of helminths, an approach termed controlled helminth infection, have been conducted in ulcerative colitis, Crohn's disease, multiple sclerosis, metabolic disease, coeliac disease and asthma, with therapeutic success. [8][9][10][11][12][13][14][15] Prominent hypotheses used to explain the protective effects of helminths include the so-called hygiene hypothesis and more specifically the 'old friends' hypothesis. These propose that certain microorganisms protect against disease and that their loss from the human microbiota due to over-sanitisation has led to increased incidence of autoimmune, allergic and metabolic diseases.…”