Safety and Feasibility of Minocycline in the Treatment of Traumatic Brain Injury (TBI)

NCT01058395 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: #H133A080044 -01IND# 104298
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is:

1. 1.To assess the safety and feasibility of minocycline administration after TBI in a dose escalation study at two different doses over 7 days.
2. 2.To assess the pharmacokinetic characteristics of two different dosing regimens of minocycline in TBI patients, the effect on biochemical markers of neuroprotective mechanisms, and effect on neurobehavioral and functional outcome.
3. 3.To begin initial assessment of the efficacy of minocycline as a therapeutic agent for severe human TBI.

Conditions

Traumatic Brain Injury

Keywords

Traumatic Brain Injury; Minocycline; Outcome

Outcome Measures

Primary Outcomes (1)

• Disability Rating Scale

  The main outcome measure after the safety data was the Disability Rating Scale (DRS). It is a 29 point scale with 29 being a severe vegetative state. It is reliable across time and demonstrates better sensitivity than the Glasgow Outcome Scale.It has been a standard primary outcome measure for most pharmaceutical studies for TBI, and was required by the FDA for the IND approval.

  4 weeks and 3 months

Secondary Outcomes (1)

• Drug Levels

  4 days after start

Study Arms (2)

800 mg loading then 200 mg Q12

EXPERIMENTAL

Minocycline 800 mg. loading followed by 200 mg. Q 12 hours.

Drug: Minocycline

800 mg loading then 400 mg Q12

EXPERIMENTAL

Minocycline 800 mg. loading followed by 400 mg. Q 12 hours.

Drug: Minocycline

Interventions

Minocycline DRUG

Minocycline 800 mg loading followed by 200 mg Q12 or Minocycline 800 mg loading followed by 400 mg Q12 will be delivered in an open-label study for seven days intravenously in one of two different dosing tiers to assess safety and toxicity per FDA recommendations. There will be tow different arms or groups differing by the amount of minocycline given over 7 days.

Also known as: Minocin

800 mg loading then 200 mg Q12; 800 mg loading then 400 mg Q12

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male , 18 to 75 years of age, irrespective of race;
• Ability to provide written informed consent or have legal representative provide written informed consent;
• Must be enrolled in the study within 6 of injury and meet the following criteria:
• GCS score of 12 or less within the first 4 hours of injury;
• Evidence of neurological injury on computer tomography (CT) of the head;
• No known allergy to minocycline or other contraindication to receiving this medication.
• Presence of central venous catheter;
• Participants must not have a known life-threatening disease prior to the brain injury: However, individuals with a stable medical illness in the opinion of the investigator may be allowed to enter the study;
• Participants are not to be on any other interventional studies aimed at enhancing neurorecovery;
• Participants are not to be receiving immunosuppressant agents prior to study enrollment.

You may not qualify if:

• Participant is a female;
• Participants, guardians or legal representatives who are unwilling to cooperate with the investigation;
• Participants who have received any other investigational drug within 30 days of injury;
• Participants known to have severe ischemic heart disease or congestive heart failure, myocardial infarction, spinal cord injury with ongoing deficits, cancer or any other severe illnesses that in the opinion of the investigator would affect the assessment of therapy;
• Participants with an ongoing neurological disease/condition or previous stroke or TBI;
• Known clinical sequelae of spinal cord injury;
• Massive cerebral hemisphere or brainstem hematoma, incompatible with survival;
• History of major depression requiring the use of the medication at the time of injury;
• Multiple trauma which in the opinion of the investigator, would jeopardize the assessment of therapy;
• Participants who have any type of penetrating head injury;
• Participants receiving chronic steroid treatment;
• Participants receiving isotretinoin;
• Lack of informed consent signed by either the participant or the subject's legal representative;
• Prior TBI, brain tumor, cerebral vascular event, or other stable brain insult;
• Prior history of Pseudotumor cerebri ;

Sponsors & Collaborators

• Wayne State University: lead

Study Sites (2)

Oakwood Dearborn Hospital

Dearborn, Michigan, 48124, United States

Location

Oakwood Southshore Hospital

Trenton, Michigan, 48183, United States

Location

Related Publications (1)

• Meythaler J, Fath J, Fuerst D, Zokary H, Freese K, Martin HB, Reineke J, Peduzzi-Nelson J, Roskos PT. Safety and feasibility of minocycline in treatment of acute traumatic brain injury. Brain Inj. 2019;33(5):679-689. doi: 10.1080/02699052.2019.1566968. Epub 2019 Feb 12.

  PMID: 30744442 DERIVED

MeSH Terms

Conditions

Brain Injuries, Traumatic; cyclopia sequence

Interventions

Minocycline

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Limitations and Caveats

Preliminary open label study, generally to assess the safety of the use of Minocycline at the dosages specified.

Results Point of Contact

• Title: Dr. Jay Meythaler
• Organization: Wayne State University

jmeythal@med.wayne.edu

(313) 375-7226

Study Officials

• Jay M Meythaler, MD

  Wayne State University

  PRINCIPAL INVESTIGATOR

• Kristina Freese, PA

  Wayne State University Dept. PM&R Oakwood

  STUDY DIRECTOR

• John Fath, MD

  Oakwood Hospital Dearborn, Trauma Surgery Director

  PRINCIPAL INVESTIGATOR

• Allen Lamb, DO

  Oakwood Southshore Hospital

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: January 19, 2010
• First Posted: January 28, 2010
• Study Start: February 1, 2010
• Primary Completion: September 1, 2015
• Study Completion: January 1, 2016
• Last Updated: September 17, 2018
• Results First Posted: September 17, 2018

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)