Minocycline in Neurocognitive Outcomes - Sickle Cell Disease

NCT05605366 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 2022-0375
• Study Type: interventional
• Target: 30
• Locations: 0 countries
• Sites: N/A

Brief Summary

Sickle cell disease (SCD) is a common, inherited blood disorder that primarily affects people of African Ancestry. It has a lot of complications including neurological complications. The neurological complications of SCD are particularly devastating and lead to cognitive decline even in the absence of overt brain injury. In such cases, it is thought that inflammation in the brain maybe partly responsible for the cognitive decline. The main reasons for this research study are to see 1) how safe and 2) how well minocycline works to try to stop/reverse cognitive decline in people with SCD. People with SCD are at risk for changes in their brain over time that can cause problems with learning, memory, and attention. Part of the reason for this is inflammation within the brain. Minocycline may be able to stop these brain changes by stopping this brain inflammation. Minocycline is a second-generation tetracycline antibiotic that has been shown to both inhibit neuroinflammation and improve cognitive function in a variety of neurodegenerative and psychiatric disorders but has not yet been studied in SCD. We are proposing here, a pilot double-blinded, randomized controlled trial to examine the tolerability and early efficacy of minocycline in adults with SCD at two dosing regimens (200 mg and 300 mg daily) versus placebo over one year. Participants will undergo a neuropsychological exam using the NIH Toolbox Cognition Battery at both study enrollment and exit (after one year) to assess for changes/stability of cognition. Participants will receive monthly phone calls/text messages to assess for adverse events and will be seen every three months for pill counts and routine laboratory monitoring. The primary outcome will be a comparison of adverse events across the two dosing strategies versus placebo. Early evidence for cognitive benefit will also be assessed from the results of the NIH Toolbox.

Conditions

Sickle Cell Disease; Cognitive Impairment; Cognitive Decline; Cognitive Change; Cognitive Dysfunction; Cognitive Deficit; Neuroinflammatory Response

Keywords

sickle cell disease; benign hematology; cognitive dysfunction; neuroinflammation

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability of prolonged minocycline exposure in adult patients with SCD

  No difference in frequency and/or duration of adverse events between one or both minocycline dose and placebo.

  12 months (1 year)

Secondary Outcomes (1)

• Cognitive Stability

  12 months (1 year)

Study Arms (3)

Treatment arm (1)

EXPERIMENTAL

This arm will receive 200mg of minocycline in a single capsule per day.

Drug: Minocycline

Treatment arm (2)

ACTIVE COMPARATOR

This arm will receive 300 mg of minocycline in a single capsule per day. This capsule is identical in size and appearance as the 200 mg capsule

Drug: Minocycline

Placebo

PLACEBO COMPARATOR

This arm will receive the placebo which is similar in size and appearance as the 200 mg and 300 mg capsules.

Drug: Placebo

Interventions

Minocycline DRUG

Minocycline is a second-generation tetracycline antibiotic with good central nervous system penetration and anti-neuroinflammatory effect.

Treatment arm (1); Treatment arm (2)

Placebo DRUG

This is capsule that is identical in size and appearance as the drug, but without active drug ingredient.

Placebo

Eligibility Criteria

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

You may qualify if:

• Adults (age ≥ 18 years old) with SCD (HbSS and HbS-β0thalassemia genotypes only) who are followed at the University of Cincinnati Medical Center's SCD clinic are eligible to participate. As hydroxyurea is the standard-of-care in SCD, individuals on hydroxyurea will be included

You may not qualify if:

• adults with other SCD genotypes (HbSC or HbS- β+thalassemia),
• individuals with a history of overt stroke or other known neurological disorder,
• premature birth before 30 weeks gestation,
• monthly therapy with chronic blood transfusions,
• coexisting autoimmune condition due to an elevated risk for autoimmune-related complications with tetracyclines,
• tetracycline allergy.
• Women who are pregnant or breast-feeding

Sponsors & Collaborators

• University of Cincinnati: lead

MeSH Terms

Conditions

Anemia, Sickle Cell; Cognitive Dysfunction; Cognition Disorders; Neuroinflammatory Diseases

Interventions

Minocycline

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Neurocognitive Disorders; Mental Disorders; Nervous System Diseases; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

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

Central Study Contacts

Christian Mpulumba, MD

CONTACT

513-558-2115; mpulumcm@ucmail.uc.edu

Kristine A Karkoska, MD

CONTACT

karkoska@ucmail.uc.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: October 20, 2022
• First Posted: November 4, 2022
• Study Start: June 1, 2025
• Primary Completion (Estimated): May 31, 2026
• Study Completion (Estimated): December 15, 2026
• Last Updated: December 6, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share