HARBOUR is a multisite placebo-controlled clinical trial for patients with UC to determine safety as well as to assess preferable dose of hydroxocobalamin based on urinary and plasma nitrite and nitrate levels and plasma nitrosothiol levels. We aim to determine if this reduction is sustained over time and is responsive to changes in clinical disease activity. We will be looking at biomarkers (urinary nitrite and nitrate levels and plasma nitrite, nitrate, and nitrosothiol levels) and fecal calprotectin levels as the study endpoints. Recruitment is split up into two phases, with the only differences including an increase of dosage and inclusion of flexible sigmoidoscopy for patients recruited into phase 2.

Status: Launch expected January 2022

In collaboration with Marcia Haigis, PhD and her lab at Harvard Medical School, we are investigating mitochondrial dysfunction which has been implicated in PSC & UC pathology.

Our goal is:

1. To identify a mitochondrial dysfunction and/or metabolite signature that distinguishes PSC & UC tissue from normal tissue
2.  To identify new biomarkers and/or therapeutic targets for active disease

Status: Manuscript Submitted

In collaboration with Sloan Devlin, PhD and her lab at Harvard Medical School, we are investigating the microbiome of the biliary tree to identify bacterial isolates at the genus level using 16s rRNA sequencing. This collaboration is driven by our hypothesis-based research questions.

The tissue and data collected in our biorepositories fuel the majority of our collaborations with bench researchers as well as those with industry. One of the primary responsibilities of our research assistants is collecting, processing and appropriately documenting our data and biosamples.

Currently we are conducting and/or participating in several biorepositories within the Brigham, around Boston and nation-wide.

In collaboration with Pfizer Inc. and Boston Children’s Hospital, the proposed study will leverage methods established through previous collaborations between Pfizer and BCH/BWH.  This includes methods for immunophenotyping leukocytes isolated from DMSO-frozen intestinal biopsies using CyTOF, transcriptomic analysis using bulk RNAseq, and microbiome analysis using 16S rRNA sequencing.  Results of each of these readouts distinguished IBD patient samples from those of healthy controls.

The current collaboration will utilize these established protocols to examine the influence of CD-associated polymorphisms on the composition and activation state of tissue-infiltrating leukocytes. Importantly, we will also profile intestinal epithelial cells in biopsies from inflamed and non-inflamed sites, and address the influence of CD-associated polymorphisms on the cellular composition of the epithelial barrier.

Management of Crohn’s disease is limited by the capacity to provide early treatment for a flare.  Early detection of inflammation and symptom severity stratification in patients with Crohn’s disease (CD) is an essential aspect of effective clinical management.  Traditionally evaluations involve consultation with specialists and testing includes blood, fecal, radiographic, and endoscopic tests.  A broader set of other characteristics likely reflect disease activity, such as physical activity, vital signs, and sleep quality in addition to more conventional parameters such as frequency of bowel movements.  Efforts at remote monitoring of Crohn’s patients have been very limited to date.  The extent and quality of the data that can be collected is limited in part by the requirement of having a device directly connected or carried by the individual being monitored.  Developing wireless digital-biomarkers capable of early detection of changes in inflammatory status including hydration status, bowel movement frequency which are recognized to correlate with inflammation stand to transform our capacity to provide early detection systems of flares and provide unique insight into the behavioral manifestations of CD.

Status: Actively recruiting

The lives of patients can be profoundly affected by inflammatory bowel disease (IBD), which includes Crohn’s disease and ulcerative colitis.  The disease must be continually monitored and managed, as acute flares of disease can be incapacitating. Treatment of complex disease may require expensive medications, and patients with uncontrolled disease may have increased visits to the emergency room, greater frequency of hospitalizations, and greater likelihood of surgery.  Disease morbidity is likely a result of many factors, including disease severity, but also nutrition, psychosocial issues including anxiety and depression, and how well patients cope with stress.

As a result, we have created outpatient interventions available to patients in the community to address modifiable factors which may impact disease morbidity and healthcare utilization.  Such factors include nutrition, stress management, anxiety and depression, and lifestyle issues such as smoking, exercise and sleep, among others. In order to address these issues, we have compiled a team that includes healthcare providers, a social worker, a psychiatrist, a nurse practitioner with stress management/resiliency expertise, a nutritionist, a nurse with IBD expertise, and a health coach, to provide comprehensive care for patients with inflammatory bowel disease.

SHIP is a multisite placebo-controlled, dose-escalating clinical trial that aims to see if sulfasalazine can help treat people with PSC. There are currently no treatment options for PSC; however, sulfasalazine is FDA approved for the treatment of CD and UC. Patients take increasing dosages of sulfasalazine/placebo throughout the trial and have the option to enter an open-label extension at the end of the trial (all subjects in the OLE will get sulfasalazine and will begin at the initial dose and then will escalate again). The primary endpoints for this study are reduction in mean ALP to < 1.5 ULN and normalization of ALP. Secondary endpoints include mean changes in other labs (e.g. LFTs, CRP, etc.) and in clinical indices such as Mayo PSC Risk Score.

Status: Actively recruiting across the US

 DOLPHIN is a multisite placebo-controlled clinical trial for patients with PSC to determine safety as well as to assess preferable dose & route of administration, comparing oral and IV doses of hydroxocobalamin. We aim to determine if this reduction is sustained over time and is responsive to changes in clinical disease activity. We will be looking at biomarkers (urinary nitrite and nitrate levels and plasma nitrite, nitrate, and nitrosothiol levels) and fecal calprotectin levels as the study endpoints.

Status: Launch expected January 2022

In collaboration with UC Davis (Dr. Christopher Bowlus ). Patients will be enrolled in an intensive 8-week diet intervention randomized either to the Vegan group or the Specific Carbohydrate Diet (SCD) group. Intervention will include video visits with a nutritionist to provide nutritional coaching on each diet. Primary endpoints of the study are to assess disease fluctuation from diet (including but not limited to Alkaline Phosphatase levels, liver biopsies, food diary, etc). Secondary endpoints include assessment of the feasibility of such a diet trial for a more extensive, possibly longer future diet trial.

Status: Closed to Recruitment, Analyzing Data

The relationship between nutrition and Primary Sclerosing Cholangitis (PSC) is complex and little is known about it. Diet may have an impact on PSC and/or Ulcerative Colitis (UC), but this has not been well established. We would like to learn more about the relationship between diet, PSC and UC. We hypothesize that patients with PSC and UC will have a larger intake of taurine than patients with UC only.  Taurine conjugated bile salts are increased in PSC and excess taurine is excreted in bile.  Taurine may be implicated in PSC as the sulfur component is a building block of hydrogen sulfide. Participants will complete two questionnaires that take about 20-25 minutes total. The first is a one-page medical history questionnaire to assess IBD and/or PSC status, medical usage, etc. The second is a Food Frequency Questionnaire (FFQ) that gives an average annual nutrient intake level for each patient.

Status: Actively recruiting across the US

In collaboration with Marcia Haigis, PhD and her lab at Harvard Medical School, we are investigating mitochondrial dysfunction which has been implicated in PSC & UC pathology.

Our goal is:

1. To identify a mitochondrial dysfunction and/or metabolite signature that distinguishes PSC & UC tissue from normal tissue
2.  To identify new biomarkers and/or therapeutic targets for active disease

Status: Manuscript Submitted

In collaboration with Sloan Devlin, PhD and her lab at Harvard Medical School, we are investigating the microbiome of the biliary tree to identify bacterial isolates at the genus level using 16s rRNA sequencing. This collaboration is driven by our hypothesis-based research questions.

The tissue and data collected in our biorepositories fuel the majority of our collaborations with bench researchers as well as those with industry. One of the primary responsibilities of our research assistants is collecting, processing and appropriately documenting our data and biosamples.

Currently we are conducting and/or participating in several biorepositories within the Brigham, around Boston and nation-wide.

In collaboration with Giovanni Traverso, MD-PhD and his lab at MIT, we are developing sulfasalazine-loaded nanoparticles to directly target drug to the liver.