Trial Outcomes & Findings for Attenuation of Corticosteroid Induced Hippocampal Changes (NCT NCT01656187)

Last Updated: 2019-03-29

Results Overview

Hopkins Verbal Learning Test-Revised (HVLT-R) is a word memory test that contains 12 nouns that are read to a participant for three consecutive trials. After each trial, a participant is asked to recall the words that were read to them. The number of words recalled on each trial is summed together to produce a total score. The total score (higher score means a better outcome) is converted to a standardized "T" score using normative data. The possible "T" score for each participant ranges from 20 to 80, with higher scores indicative of a better outcome.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

46 participants

Primary outcome timeframe

Baseline and 24 weeks

Results posted on

2019-03-29

Participant Flow

73 patients were screened for eligibility between May 2012 and January 2016.

46 of 73 participants were randomized. Of those not randomized, 27 did not meet inclusion criteria.

Participant milestones

Participant milestones
Measure	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	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.
First Intervention (24 Weeks) STARTED	20	26
First Intervention (24 Weeks) COMPLETED	14	23
First Intervention (24 Weeks) NOT COMPLETED	6	3
Washout (4 Weeks) STARTED	14	23
Washout (4 Weeks) COMPLETED	14	22
Washout (4 Weeks) NOT COMPLETED	0	1
Second Intervention (24 Weeks) STARTED	14	22
Second Intervention (24 Weeks) COMPLETED	13	19
Second Intervention (24 Weeks) NOT COMPLETED	1	3

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Attenuation of Corticosteroid Induced Hippocampal Changes

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Memantine, Then Placebo n=20 Participants Participants received Memantine 10 mg capsule twice/day for 24 weeks, then underwent a 4-week washout period, then received memantine-matched placebo capsule twice/day for 24 weeks. Memantine oral capsule was initiated at 5 mg/day at Week 0, then titrated to 5 mg twice/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/day 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 oral Placebo capsule was initiated at 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 n=26 Participants Participants received Placebo capsule (matching Memantine 10 mg capsule) twice/day for 24 weeks. After a washout period of 4 weeks, they received Memantine 10 mg capsule twice a day for 24 weeks. Memantine oral capsule was initiated at 5 mg/day at 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 oral Placebo capsule was initiated at 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).	Total n=46 Participants Total of all reporting groups
Age, Continuous	43.10 years STANDARD_DEVIATION 12.07 • n=5 Participants	43.42 years STANDARD_DEVIATION 12.72 • n=7 Participants	43.28 years STANDARD_DEVIATION 12.30 • n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants	8 Participants n=7 Participants	19 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	18 Participants n=7 Participants	27 Participants n=5 Participants
Region of Enrollment United States	20 participants n=5 Participants	26 participants n=7 Participants	46 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and 24 weeks

Population: All participants who received at least one dose of each intervention and completed all study visits were included in the analysis. Participants who dropped out during the washout period (between Weeks 24-28) did not receive the second intervention and were not included in the analysis.

Outcome measures

Outcome measures
Measure	Memantine n=42 Participants Participants who received Memantine 10 mg capsule twice per day in either the first or last 24 weeks of the study.	Placebo n=40 Participants Participants who received placebo capsule (matching Memantine 10 mg) twice per day in either the first or last 24 weeks of the study.
Hopkins Verbal Learning Test-Revised (HVLT-R) Total Score HVLT Total Score at Baseline	39.40 units on a scale Standard Deviation 1.82	36.93 units on a scale Standard Deviation 1.72
Hopkins Verbal Learning Test-Revised (HVLT-R) Total Score HVLT Total Score at 24 weeks	37.67 units on a scale Standard Deviation 1.61	38.37 units on a scale Standard Deviation 1.92

Adverse Events

Memantine

Serious events: 5 serious events

Other events: 8 other events

Deaths: 0 deaths

Placebo

Serious events: 12 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Memantine n=42 participants at risk Participants who received Memantine 10 mg capsule twice per day for 24 weeks.	Placebo n=40 participants at risk Participants who received Placebo capsule (matching Memantine 10 mg capsule) twice per day for 24 weeks.
Gastrointestinal disorders Abnormal stool color	2.4% 1/42 • 24 weeks for each intervention. The safety population included all participants who received at least one dose of intervention.	0.00% 0/40 • 24 weeks for each intervention. The safety population included all participants who received at least one dose of intervention.
Injury, poisoning and procedural complications Concussion	2.4% 1/42 • 24 weeks for each intervention. The safety population included all participants who received at least one dose of intervention.	0.00% 0/40 • 24 weeks for each intervention. The safety population included all participants who received at least one dose of intervention.
Vascular disorders Elevated blood pressure	2.4% 1/42 • 24 weeks for each intervention. The safety population included all participants who received at least one dose of intervention.	0.00% 0/40 • 24 weeks for each intervention. The safety population included all participants who received at least one dose of intervention.
Vascular disorders Low blood pressure	4.8% 2/42 • 24 weeks for each intervention. The safety population included all participants who received at least one dose of intervention.	0.00% 0/40 • 24 weeks for each intervention. The safety population included all participants who received at least one dose of intervention.
Gastrointestinal disorders Nausea	0.00% 0/42 • 24 weeks for each intervention. The safety population included all participants who received at least one dose of intervention.	2.5% 1/40 • 24 weeks for each intervention. The safety population included all participants who received at least one dose of intervention.
Reproductive system and breast disorders Pregnancy	2.4% 1/42 • 24 weeks for each intervention. The safety population included all participants who received at least one dose of intervention.	0.00% 0/40 • 24 weeks for each intervention. The safety population included all participants who received at least one dose of intervention.
Nervous system disorders Tremor	2.4% 1/42 • 24 weeks for each intervention. The safety population included all participants who received at least one dose of intervention.	0.00% 0/40 • 24 weeks for each intervention. The safety population included all participants who received at least one dose of intervention.
Blood and lymphatic system disorders Elevated blood glucose	2.4% 1/42 • 24 weeks for each intervention. The safety population included all participants who received at least one dose of intervention.	0.00% 0/40 • 24 weeks for each intervention. The safety population included all participants who received at least one dose of intervention.

Additional Information

E. Sherwood Brown, MD, PhD

UT Southwestern Medical Center

Phone: 214-645-6950

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Memantine n=42 participants at risk Participants who received Memantine 10 mg capsule twice per day for 24 weeks.	Placebo n=40 participants at risk Participants who received Placebo capsule (matching Memantine 10 mg capsule) twice per day for 24 weeks.
Renal and urinary disorders Fournier's gangrene	2.4% 1/42 • 24 weeks for each intervention. The safety population included all participants who received at least one dose of intervention.	0.00% 0/40 • 24 weeks for each intervention. The safety population included all participants who received at least one dose of intervention.
Respiratory, thoracic and mediastinal disorders Asthma exacerbation	2.4% 1/42 • 24 weeks for each intervention. The safety population included all participants who received at least one dose of intervention.	0.00% 0/40 • 24 weeks for each intervention. The safety population included all participants who received at least one dose of intervention.
Infections and infestations C. difficile	2.4% 1/42 • 24 weeks for each intervention. The safety population included all participants who received at least one dose of intervention.	0.00% 0/40 • 24 weeks for each intervention. The safety population included all participants who received at least one dose of intervention.
Cardiac disorders Chest pain	0.00% 0/42 • 24 weeks for each intervention. The safety population included all participants who received at least one dose of intervention.	2.5% 1/40 • 24 weeks for each intervention. The safety population included all participants who received at least one dose of intervention.
Gastrointestinal disorders Constipation	0.00% 0/42 • 24 weeks for each intervention. The safety population included all participants who received at least one dose of intervention.	2.5% 1/40 • 24 weeks for each intervention. The safety population included all participants who received at least one dose of intervention.
Ear and labyrinth disorders Ear infection	2.4% 1/42 • 24 weeks for each intervention. The safety population included all participants who received at least one dose of intervention.	0.00% 0/40 • 24 weeks for each intervention. The safety population included all participants who received at least one dose of intervention.
Musculoskeletal and connective tissue disorders Gout flare	0.00% 0/42 • 24 weeks for each intervention. The safety population included all participants who received at least one dose of intervention.	2.5% 1/40 • 24 weeks for each intervention. The safety population included all participants who received at least one dose of intervention.
Endocrine disorders Hypokalemia	0.00% 0/42 • 24 weeks for each intervention. The safety population included all participants who received at least one dose of intervention.	2.5% 1/40 • 24 weeks for each intervention. The safety population included all participants who received at least one dose of intervention.
Injury, poisoning and procedural complications Lumbar spine injury	0.00% 0/42 • 24 weeks for each intervention. The safety population included all participants who received at least one dose of intervention.	2.5% 1/40 • 24 weeks for each intervention. The safety population included all participants who received at least one dose of intervention.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ovarian cyst	0.00% 0/42 • 24 weeks for each intervention. The safety population included all participants who received at least one dose of intervention.	2.5% 1/40 • 24 weeks for each intervention. The safety population included all participants who received at least one dose of intervention.
Respiratory, thoracic and mediastinal disorders Pneumonia	2.4% 1/42 • 24 weeks for each intervention. The safety population included all participants who received at least one dose of intervention.	0.00% 0/40 • 24 weeks for each intervention. The safety population included all participants who received at least one dose of intervention.
Musculoskeletal and connective tissue disorders Right shoulder pain	0.00% 0/42 • 24 weeks for each intervention. The safety population included all participants who received at least one dose of intervention.	2.5% 1/40 • 24 weeks for each intervention. The safety population included all participants who received at least one dose of intervention.
Infections and infestations Shingles	0.00% 0/42 • 24 weeks for each intervention. The safety population included all participants who received at least one dose of intervention.	2.5% 1/40 • 24 weeks for each intervention. The safety population included all participants who received at least one dose of intervention.
Skin and subcutaneous tissue disorders Lupus flare	0.00% 0/42 • 24 weeks for each intervention. The safety population included all participants who received at least one dose of intervention.	2.5% 1/40 • 24 weeks for each intervention. The safety population included all participants who received at least one dose of intervention.
Injury, poisoning and procedural complications Tooth fracture	2.4% 1/42 • 24 weeks for each intervention. The safety population included all participants who received at least one dose of intervention.	0.00% 0/40 • 24 weeks for each intervention. The safety population included all participants who received at least one dose of intervention.
Renal and urinary disorders Urinary tract infection	0.00% 0/42 • 24 weeks for each intervention. The safety population included all participants who received at least one dose of intervention.	5.0% 2/40 • 24 weeks for each intervention. The safety population included all participants who received at least one dose of intervention.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Vulvar squamous cell carcinoma	0.00% 0/42 • 24 weeks for each intervention. The safety population included all participants who received at least one dose of intervention.	2.5% 1/40 • 24 weeks for each intervention. The safety population included all participants who received at least one dose of intervention.