Study of Immunomodulation Using Naltrexone and Ketamine for COVID-19
Condition: COVID-19; Acute Respiratory Distress Syndrome; Severe Acute Respiratory Syndrome (SARS); Coronavirus Infections
MeSH terms: COVID-19; Coronavirus Infections; Severe Acute Respiratory Syndrome; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury; Syndrome
Intervention: Naltrexone; Ketamine; Placebo
Intervention description: Low dose naltrexone, 4.5 mg by mouth, given from date of admission through time participant is stable for discharge for inpatient participants with mild/moderate COVID-19 infection stages. Naltrexone will continue for 1 month post hospital discharge. Patients progressing to requirement for advanced oxygenation will be reassess when sedation and assigned to Ketamine arm. Naltrexone may be reduced to 1.5 mg/day if interfering with sedation and can be held when sedation and symptoms of withdrawal is an issue..; Low dose ketamine hydrochloride given intravenously at a dosage of 0.15 mg/kg body weight for maximum 20 mg every 6 hours, to inpatient participants with advanced oxygenation requirements from either time of admission or time of progression of mild/moderate disease until time participant is stable for discharge, as a rescue treatment. If patient is transferred from the naltrexone or placebo arm, they will continue to receive naltrexone/placebo. Dosage of ketamine may be increased to 0.3 mg/kg body weight, maximum 30 mg every 6 hours, if participant does not respond at the lower dosage. Ketamine can be reduced back to 0.15 mg/kg at the clinical decision of the investigator and when patient has hypertensive emergency, the dose can be held until hypertensive emergency is controlled.; Oral placebo, given from date of admission through time participant is stable for discharge for inpatient participants in mild/moderate COVID-19 infection stages. Placebo will continue for 1 month post discharge. Participants progressing to requirement for advanced oxygenation will be reassigned to Ketamine arm.
Intervention MeSH terms: Naltrexone; Ketamine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Factorial Assignment
Intervention model description: Prospective, single center, randomized, double blinded study of naltrexone with an open label extension using ketamine as a rescue drug for patients who progress in their disease
Masking: Triple (Participant, Care Provider, Investigator)
Masking description: No other parties blinded
Enrollment: 70.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: naltrexone; ketamine; cytokine storm; Interleukin-2; therapeutic treatment

Summary:

      Ideal new treatments for Novel Coronavirus-19 (COVID-19) would help halt the progression
      disease in patients with mild disease prior to the need for artificial respiration
      (ventilators), and also provide a rescue treatment for patients with severe disease, while
      also being affordable and available in quantities sufficient to treat large numbers of
      infected people. Low doses of Naltrexone, a drug approved for treating alcoholism and opiate
      addiction, as well as Ketamine, a drug approved as an anesthetic, may be able to interrupt
      the inflammation that causes the worst COVID-19 symptoms and prove an effective new
      treatment. This study will investigate their effectiveness in a randomized, blinded trial
      versus standard treatment plus placebo.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Positive for COVID -19

          -  Admitted to Beaumont Hospital - Royal Oak, Michigan

          -  Age ≥18

          -  Receiving ≤ 6 liters/minute oxygen by nasal cannula for randomization to either
             placebo or naloxone arm OR receiving ≥ 6 liters/minute oxygen by nasal cannula or
             requiring advanced oxygenation for placement in ketamine arm

        Exclusion Criteria:

          -  Known allergy to naltrexone

          -  Known allergy to ketamine

          -  Diagnosis of schizophrenia or psychosis

          -  Pregnancy based on available medical history, existing labs, or verbal report

          -  On chronic high dose opioids > 90mg morphine mg equivalence

          -  Use of naltrexone or Vivitrol within 90 days