Attenuation of Corticosteroid Induced Hippocampal Changes

NCT ID: NCT01656187

Last Updated: 2019-03-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 46 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-01-31
• Study Completion Date: 2017-01-31

Brief Summary

The purpose of the study is to determine if an investigational drug called memantine,used here as add-on therapy, is associated with improvements in memory, mood and asthma symptoms. We will also examine changes in the brain by taking images or pictures using an MRI/MRS.

Detailed Description

A total of 50 outpatients receiving chronic oral corticosteroid therapy will be enrolled in a 52-week randomized, double-blind, placebo-controlled, crossover trial of memantine. Participant will receive either memantine or a placebo for 24 weeks. They have an equal chance of receiving memantine or placebo. After 24 weeks they will discontinue all study medication for 4 weeks. This process will be repeated one additional time in the study and the participant will crossed-over to either memantine or placebo, whichever the participant did not receive before, so they will have taken both placebo and memantine during one of these courses.

Randomization will be stratified by prednisone dose of < 20 mg/day vs. ≥ 20 mg/day. Memantine or placebo starting at 5 milligrams once a day, increased to 5 milligrams twice a day (10 total) at week 2, 15 milligrams total at week 3, and 20 milligrams total from weeks 4-24 unless side effects require the study doctor to increase the initial doses slower than described above or reduce the dose. This same process will be repeated at week 28 after the participant have been completely off of study medication for 4 weeks. Structural MRI and 1HMRS will be obtained at baseline and weeks 24 and 52 (after memantine and placebo).

The clinician version of the structured Clinical Interview for DSM-IV (SCID) is a brief structured interview for major Axis I disorders in DSM-IV including major depressive disorder, dysthymic disorder, bipolar disorders, psychotic disorders, anxiety disorders, eating disorders, and alcohol and substance abuse/dependence. This will be given at baseline to screen for illnesses with CNS involvement or cognitive impairment. Blood draws will be performed at baseline to assess insulin and fasting glucose levels.

Each participant will then return for follow-up appointments as scheduled and repeat outcome measures. Pill counts will be conducted, and a list of current medications and doses will be obtained at each visit. Participants will be evaluated by both the RA and PI at each follow-up appointment.

The HVLT-R will be given at baseline, and weeks 12, 24, 28, 40, and 52; this will be the primary outcome measure. Other cognitive assessments will be performed at these same visits as well.

Conditions

Organic Memory Impairment

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Memantine, Then Placebo

Participants first received Memantine 10 mg capsule twice a day for 24 weeks. After a washout period of 4 weeks, they then received Placebo capsule (matching Memantine 10 mg capsule) twice a day for 24 weeks.

Group Type: EXPERIMENTAL

Memantine 10 mg capsule

Intervention Type: DRUG

Memantine oral capsule was initiated at 5 mg/day at Randomization (Week 0), then titrated to 5 mg twice a day at Week 2, then increased to 10 mg in the morning and 5 mg in the evening at Week 3, and then to 10 mg twice a day (intervention dose) at Weeks 4-24. For the participants in the "Placebo, then Memantine" arm, the same titration schedule was maintained after the 4-week washout period (Week 28-52).

Memantine-matched Placebo capsule

Intervention Type: DRUG

Memantine-matched oral Placebo capsule was initiated at Randomization (Week 0) and maintained Weeks 0-24 in a manner consistent with the active drug titration schedule. The number of placebo capsules matched the number of active drug capsules at each titration checkpoint. For the participants in the "Memantine, then Placebo" arm, the same titration schedule was maintained after the 4-week washout period (Week 28-52).

Placebo, Then Memantine

Participants first received Placebo capsule (matching Memantine 10 mg capsule) twice a day for 24 weeks. After a washout period of 4 weeks, they then received Memantine 10 mg capsule twice a day for 24 weeks.

Group Type: EXPERIMENTAL

Memantine 10 mg capsule

Intervention Type: DRUG

Memantine oral capsule was initiated at 5 mg/day at Randomization (Week 0), then titrated to 5 mg twice a day at Week 2, then increased to 10 mg in the morning and 5 mg in the evening at Week 3, and then to 10 mg twice a day (intervention dose) at Weeks 4-24. For the participants in the "Placebo, then Memantine" arm, the same titration schedule was maintained after the 4-week washout period (Week 28-52).

Memantine-matched Placebo capsule

Intervention Type: DRUG

Memantine-matched oral Placebo capsule was initiated at Randomization (Week 0) and maintained Weeks 0-24 in a manner consistent with the active drug titration schedule. The number of placebo capsules matched the number of active drug capsules at each titration checkpoint. For the participants in the "Memantine, then Placebo" arm, the same titration schedule was maintained after the 4-week washout period (Week 28-52).

Interventions

Memantine 10 mg capsule

Memantine oral capsule was initiated at 5 mg/day at Randomization (Week 0), then titrated to 5 mg twice a day at Week 2, then increased to 10 mg in the morning and 5 mg in the evening at Week 3, and then to 10 mg twice a day (intervention dose) at Weeks 4-24. For the participants in the "Placebo, then Memantine" arm, the same titration schedule was maintained after the 4-week washout period (Week 28-52).

Intervention Type: DRUG

Memantine-matched Placebo capsule

Memantine-matched oral Placebo capsule was initiated at Randomization (Week 0) and maintained Weeks 0-24 in a manner consistent with the active drug titration schedule. The number of placebo capsules matched the number of active drug capsules at each titration checkpoint. For the participants in the "Memantine, then Placebo" arm, the same titration schedule was maintained after the 4-week washout period (Week 28-52).

Intervention Type: DRUG

Other Intervention Names

Namenda; Sugar pill

Eligibility Criteria

Inclusion Criteria

• Diagnosis of any chronic medical condition requiring treatment with oral corticosteroids confirmed by chart review and/or patient assessment by Dr. Khan (co-I).
• Receiving prednisone therapy of at least 5 mg of prednisone/day for at least 6 months with anticipated treatment for ≥ 12 additional months.
• Age 18-65 years.
• Baseline CVLT-II total T score ≤ 54.

Exclusion Criteria

• Illnesses associated with CNS involvement (e.g., seizures, brain tumors, head injury with loss of consciousness) or cognitive impairment (e.g., substance dependence within the past 2 years, bipolar disorder) Potential participants with mood symptoms secondary to corticosteroids (based on SCID) will not be excluded because this could selectively exclude subjects who are sensitive to the CNS effects of corticosteroids.
• Vulnerable populations (e.g. severe cognitive impairment, pregnant or nursing women, prisoners).
• Severe or life-threatening medical illness that would make completion of study unlikely
• Contraindications to memantine therapy (e.g. severe side effects in the past)
• Danger to self or others as defined by > 1 lifetime suicide attempt or assault, any suicide attempt or assault within the past year, and active suicidal or homicidal ideation with plan and intent.
• Metal implants, claustrophobia, or other contraindications to MRI

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute on Drug Abuse (NIDA)

NIH

Sponsor Role: collaborator

University of Texas Southwestern Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sherwood Brown, PhD, MD

Role: PRINCIPAL_INVESTIGATOR

UT Southwestern Medical Center

Locations

Aston Ambulatory Care Center, Allergy and Immunology

Dallas, Texas, United States

Countries

United States

Other Identifiers

1R01DA029596

Identifier Type: NIH

Identifier Source: secondary_id

View Link

032011-007

Identifier Type: -

Identifier Source: org_study_id