Corticosteroids to Reduce Inflammation in Severe Pancreatitis (CRISP)

 

Co-investigators:

• Michael Donnino
• Steve Freedman
• Kate Berg
• Michael Cocchi
• Anne Grossestruer
• Lakshman Balaji
• Xiaowen Liu
• Noa Berlin
• Jacob Vine
• Ankit Chhoda

Study Staff

• Franklin Li
• Shivani Mehta
• Neeharika Munjal
• Jeremy Silverman

Abstract

Pancreatitis is a common and potentially lethal and/or debilitating condition for which existing treatment options have shown limited efficacy. Since inflammation is a key driver of disease progression in pancreatitis, we propose to conduct a Phase II randomized clinical trial to establish if a brief course of anti-inflammatory corticosteroids given very early in the acute process will improve key clinical outcomes including illness severity, inflammation and pancreatic injury, hospital and ICU-free days, and death. Successful trial outcomes will set the stage for a larger multi-site Phase III trial and potentially lead to a new and effective treatment option for pancreatitis.

Thiamine as Adjunctive Therapy for Diabetic Ketoacidosis

Description

Principal Investigator:

Michael Donnino

Status of Study:

Enrolling

Purpose of Protocol:

To study if vitamin B1 (thiamine) is able to more rapidly reverse diabetic ketoacidosis.

Specific Aim #1: To determine whether thiamine will more rapidly reverse acidosis and reduce hospital length of stay in patients with DKA

Specific Aim #2: To evaluate whether the administration of thiamine to patients with DKA results in increased cellular oxygen consumption and preservation of β-cell function

Significance and Background:

Diabetic Ketoacidosis (DKA) is a potentially life-threatening disorder that may also expose patients to overt or sub-clinical morbidity. Even with optimal preventative strategies, a subset of patients will inevitably continue to develop DKA. Thiamine is an essential co-factor for several key enzymes of metabolism including pyruvate dehydrogenase (gatekeeper for Krebs Cycle). Thiamine deficiency is well known to result in lactic acidosis secondary to impaired aerobic metabolism and is a causal component of neurological and memory disorders, specifically the Wernicke-Korsakoff Syndrome. Moreover, glucose loading has been described as a precipitant of thiamine deficiency and we have demonstrated that metabolic stress can deplete thiamine levels over time.

We hypothesize that the provision of intravenous thiamine to patients with DKA will serve as adjunctive measure to more rapidly reverse acidosis and will improve cellular oxygen consumption.

Design:

Prospective, randomized, double-blind, placebo-controlled phase II human clinical trial.

Inclusion Criteria:

1. Bicarbonate ≤15 mEq/L
2. Anion gap > 12 mEq/L
3. Blood pH≤ 7.24 (if already obtained by clinical team)
4. Urine ketones (qualitative) or serum ketones (β-hydroxybutyric acid) > 3 mmol/L
5. Enrollment within 6 hours of presentation

Exclusion Criteria:

1. Current thiamine supplementation ≥ 6 milligrams per day (i.e., more than a multivitamin)
2. Competing causes of severe acidosis including seizure, carbon monoxide poisoning, cyanide toxicity, cardiac arrest, liver dysfunction (specifically defined as known cirrhosis)
3. Known allergy to thiamine
4. Competing indication for thiamine administration as judged by the clinical team (e.g., alcoholic)
5. Research-protected populations (pregnant women, prisoners, the intellectually disabled)
6. Patient enrolled previously in same study
7. Code status of Do Not Resuscitate/Do Not Intubate (DNR/DNI) or Comfort Measures Only (CMO)

Treatment Protocol:

Patients will be administered the study drug intravenously (placebo or 200 mg thiamine in normal saline) and will receive a dose every 12 hours for two days.

Outcomes:

The primary outcome is the change in bicarbonate over the 24 hours following enrollment.

Secondary outcomes will include change in anion gap, change in lactate, ICU length of stay, hospital length of stay, and hospital resource utilization. Additionally, measurement of oxygen consumption in circulating mononuclear cells will be obtained as an index of whole body oxidative glucose metabolism.

Measurements:

All patients enrolled in the study will have blood drawn at time 0 hours, 6 hours, 12 hours, 18 hours and 24 hours.  We will measure bicarbonate at each time point through the clinical lab. In addition, blood samples will be analyzed for lactate, anion gap, albumin, and thiamine level.

MIND BODY INTERVENTION FOR THE TREATMENT OF CHRONIC PAIN

 

Overview: The purpose of this study is to see if mind-body approaches will help to reduce pain and suffering in people with chronic back pain. Mind-body approaches are behavioral treatments focused on breaking the pain-generating cycle between the mind and body. We are doing this study because people with chronic pain often continue to suffer after traditional interventions such as medications, surgery, and/or physical therapy. Other researchers have tried various approaches to teach those suffering from chronic pain how to break this vicious connection between the mind and body, with varying degrees of success. We intend to see if new approaches using a mind-body intervention will improve pain symptoms particularly when other therapies have not worked.

About Our Benefactor: We thank Adam D'Angelo for providing the funding for this trial.

If you are interested in being part of the study, please contact us at 617-754-2884 or mindbodystudy@bidmc.harvard.edu

Epinephrine in the Pediatric Intensive Care Unit: A Dose-Effect Trial (EPIDose)

Principal Investigator - Dr. Catherine Ross

Study Staff

• Muhammad Asad

Starting in Winter 2023, pediatric intensive care unit (ICU) patients at Boston Children’s Hospital may be eligible for the EPI Dose Study. This innovative study investigates using two commonly used doses of epinephrine to treat sudden low blood pressure. Since very low blood pressure is an emergency that is difficult to predict, this study has been approved by the BCH IRB to use a special consent process for this potentially life-saving intervention. Learn more by visiting the Epi Dose Study page or by visiting clinicaltrials.gov.

This study is led by Dr. Catherine Ross, MD, at Boston Children Hospital, and is funded by the National Institutes of Health (NIH).