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Intranasal Heparin Tolerability Study

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ClinicalTrials.gov Identifier: NCT04490239
Recruitment Status : Completed
First Posted : July 29, 2020
Results First Posted : April 28, 2021
Last Update Posted : April 30, 2021
Sponsor:
Information provided by (Responsible Party):
Joshua Sharp, University of Mississippi, Oxford

Brief Summary:

The investigators are investigating the tolerability of Heparin Sodium (porcine) administered topically via a nasal spray. This agent is being investigated as a potential prophylactic treatment to prevent infection by SARS(severe acute respiratory syndrome)-CoV-2, the novel coronavirus that causes COVID-19. Heparin Sodium (porcine) is an FDA-approved anticoagulant drug administered by injection. Recent work from multiple groups have found that heparin can prevent the infection of cells by SARS-CoV-2, indicating a possible use as a topical anti-viral. Numerous studies in both rodent models and humans have shown that heparin administered via a pulmonary or intranasal route enters the blood stream in negligible amounts, suggesting intranasal administration of heparin should be safe even at very large doses. Data from mouse models indicate that repeated daily nasal administration of heparin had no adverse effects in mice over a two week period (including weight loss, nose bleeds, loss of sense of smell, nasal discharge, or decreased blood clotting time). However, no data of repeated nasal administration of heparin in humans is available.

The investigators will test nasal administration of FDA-approved heparin sodium (porcine), originally formulated for injection. The formulations the investigators will be testing consist of heparin, sodium chloride, and 1% benzyl alcohol as a preservative bottled in a nasal sprayer dispensing 0.1 mL(millilitres) per spray. The investigation is planned in two phases. A single-dose phase will test the acute tolerability of the drug. In this phase, subjects will be administered 0.1 mL of Heparin Sodium in each nostril formulated at one of two doses: Day 1 will test a formulation of 5000 U(units)/mL, and Day 2 will test a formulation of 10000 U(units) /mL. After each dose, subjects will be tested for systemic exposure via blood aPTT tests and platelet count, as well as for local topical toxicity via examination for epistaxis and anosmia, along with any other adverse events. In the chronic phase, subjects will be administered the highest dose that was tolerated in the acute phase daily for fourteen days. Subjects will be tested for aPTT and platelet count, as well as epistaxis, anosmia and any other adverse events.


Condition or disease Intervention/treatment Phase
Covid19 Drug: Intranasal heparin sodium (porcine) Early Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 6 participants
Allocation: N/A
Intervention Model: Sequential Assignment
Intervention Model Description: This study will evaluate the acute and multi-day (14 days) tolerability of intranasally administered heparin. Two doses will be tested in the acute phase: 1000 U/day, then 2000 U/day. In the multi-day phase, the highest tolerated dose from the acute phase will be tested over a 14-day period of daily self-administration.
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Intranasal Heparin Tolerability Study
Actual Study Start Date : October 9, 2020
Actual Primary Completion Date : November 18, 2020
Actual Study Completion Date : November 18, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Blood Thinners

Arm Intervention/treatment
Experimental: Experimental Arm

Subjects will be administered heparin sodium (porcine) bottled in a nasal sprayer with a volume per spray of 0.1 mL.

Acute phase:

On day 1, each subject will be administered 0.1 mL per nostril of 5000 U/mL heparin sodium (porcine), for a total dose of 1000 U. Vital signs, blood work, and follow-up clinical observation will be used to detect adverse effects.

On day 2, each subject will be administered 0.1 mL per nostril of 10000 U/mL heparin sodium (porcine), for a total dose of 2000 U. Vital signs, blood work, and follow-up clinical observation will be used to detect adverse effects.

Chronic phase:

The highest acute dose that has no impact on aPTT or INR will be used for the chronic phase of this study. Each subject will be administered a daily dose for fourteen days. The first and last dose will be administered in the clinic; all other doses will be self-administered by subjects at home at the same time of day using a dosing diary to keep records.

Drug: Intranasal heparin sodium (porcine)
Intranasal heparin sodium
Other Names:
  • NDC (National Drug Code) 0409-2721-30
  • NDC 0409-2723-01




Primary Outcome Measures :
  1. Number of Participants With Normal or Abnormal Activated Partial Thromboplastin Time (aPTT), Acute Phase Day 1 [ Time Frame: 24 hours after a 1000 U intranasal dose of heparin ]
    A measurement of blood clotting ability; tests for systemic bioavailability of intranasal heparin collected 24 hours after a 1000 U intranasal dose of heparin

  2. Number of Participants With Normal or Abnormal Activated Partial Thromboplastin Time (aPTT), Acute Phase Day 2 [ Time Frame: 24 hours after 2000 U dose intranasal heparin ]
    A measurement of blood clotting ability; tests for systemic bioavailability of intranasal heparin collected 24 hours after a 2000 U intranasal dose of heparin

  3. Number of Participants With Normal or Abnormal Activated Partial Thromboplastin Time (aPTT), Chronic Phase Day 14 [ Time Frame: Day 14, chronic phase ]
    A measurement of blood clotting ability; tests for systemic bioavailability of intranasal heparin obtained immediately after the 14 consecutive day of daily 2000 U dose of intranasal heparin

  4. Number of Participants With Normal or Abnormal Activated Partial Thromboplastin Time (aPTT), Chronic Phase Day 15 [ Time Frame: 24 hours after the last 2000 U dose of the chronic phase ]
    A measurement of blood clotting ability; tests for systemic bioavailability of intranasal heparin obtained 24 hours after the 14 consecutive day of daily 2000 U dose of intranasal heparin

  5. Percent Change in Platelet Count From Pre-dose Baseline [ Time Frame: Pre-dose baseline, Day 14 chronic phase ]
    Indicative of heparin-induced thrombocytopenia, a serious adverse side effect of systemically bioavailable heparin, measured immediately after the last 2000 U intranasal dose of the chronic phase.

  6. Number of Incidents of Epistaxis, Acute Phase [ Time Frame: Day 0 through Day 2, acute phase ]
    Number of incidents of blood coming from the nose during the acute phase

  7. Number of Incidents of Epistaxis, Chronic Phase [ Time Frame: Day 1 through Day 15, chronic phase ]
    Blood coming from the nose or pink tinged nasal secretions

  8. Number of Participants With Normal or Abnormal Platelet Counts, Chronic Phase Day 14 [ Time Frame: Day 14, Chronic Phase ]
    Abnormally low platelet counts indicative of heparin-induced thrombocytopenia, a serious adverse side effect of systemically bioavailable heparin, measured immediately after the last 2000 U intranasal dose of the chronic phase.


Secondary Outcome Measures :
  1. Other Adverse Effects, Acute Phase [ Time Frame: Day 0 through Day 2, acute phase ]
    Reports of mild, short-lived nasal irritation immediately after administration including mild burning sensation

  2. Other Adverse Effects, Chronic Phase [ Time Frame: Day 1 through Day 15, chronic phase ]
    Reports of mild, short-lived nasal irritation immediately after administration including mild burning sensation, itchiness or sneezing



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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

Normal, healthy adults aged 18 to 65 years

Exclusion Criteria:

  • Allergy to Heparin
  • Currently taking any prescription blood thinners or anti-coagulants, or currently taking any intranasal medication
  • Known history of anemia, thrombocytopenia, or other blood disorder
  • Autoimmune disorders
  • Known history of Neurologic/Psychiatric disorders
  • Report of an active infection
  • Subject is pregnant or breast-feeding, or is expecting to conceive during the study.

NOTE: Subjects will be instructed to abstain from alcohol for the duration of the study.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04490239


Locations
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United States, Mississippi
The University of Mississippi National Center for Natural Products Research
University, Mississippi, United States, 38677-1848
Sponsors and Collaborators
Joshua Sharp
Investigators
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Principal Investigator: Bill Gurley, PhD University of Mississippi Medical Center
  Study Documents (Full-Text)

Documents provided by Joshua Sharp, University of Mississippi, Oxford:
Study Protocol  [PDF] September 1, 2020
No Statistical Analysis Plan (SAP) exists for this study.

Publications:
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Responsible Party: Joshua Sharp, Associate Professor, University of Mississippi, Oxford
ClinicalTrials.gov Identifier: NCT04490239    
Other Study ID Numbers: Intranasal Heparin
First Posted: July 29, 2020    Key Record Dates
Results First Posted: April 28, 2021
Last Update Posted: April 30, 2021
Last Verified: April 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Individual participant data that underlie the results reported, after deidentification
Supporting Materials: Study Protocol
Time Frame: Beginning 3 months and ending 36 months following publication
Access Criteria: Proposals should be directed to jsharp@olemiss.edu. To gain access, requestors will need to sign a data access agreement.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Heparin
Calcium heparin
Anticoagulants
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action