Phase I/II Study of NORTHERA (DROXIDOPA) for Dysautonomia in Adult Survivors of Menkes Disease and Adults With Occipital Horn Syndrome: Double-blind Placebo-controlled Randomized Crossover Clinical Trial
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 3
- 试验地点
- 2
- 主要终点
- Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE v5 tool
研究概览
简要总结
The purpose of this study is to evaluate whether Northera (Droxidopa) is safe and effective in young adults with Menkes disease who survived the most severe complications of their illness or adults with occipital horn syndrome (OHS), who have trouble with intermittent low blood pressure and other symptoms of dysautonomia. The outcomes and information from this study may help adult survivors of Menkes disease and individuals with OHS lead more normal day-to-day lives.
详细描述
This pilot clinical trial will evaluate the safety, tolerability, dosing, and preliminary efficacy of Northera (Droxidopa) treatment in young adults who survived the major neurodegenerative and neurocognitive effects of Menkes disease through early Copper Histidinate treatment. We hypothesize that Northera (Droxidopa) in Menkes disease survivors with symptoms of dysautonomia (e.g., syncope, dizziness, orthostatic hypotension, abnormal sinoatrial conduction, nocturnal bradycardia, and bowel or bladder dysfunction) from persistent deficiency of the copper-dependent enzyme, dopamine-β-hydroxylase, will be safe, and correct or improve blood neurochemical levels, raise systolic blood pressure, and produce symptomatic improvement and better overall quality of life. We will test this hypothesis in six to ten Menkes disease survivors or OHS patients in a double-blind placebo-controlled randomized crossover clinical trial.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult persons with Menkes disease who survived beyond the expected natural history, attained independent ambulation, attend (or attended) school, and reached adulthood after early CuHis treatment for three years or adults with Occipital Horn Syndrome, who manifest clinical signs and symptoms of dysautonomia, e.g., orthostatic hypotension: specifically, a decrease in systolic or diastolic blood pressure of at least 20 or 10 mm Hg, respectively, within three minutes after standing, and/or chronic diarrhea: production of loose stools with or without increased stool frequency for more than four weeks immediately preceding enrollment.
- •History of at least thrice weekly occurrence of dizziness/feeling lightheaded while standing upright and/or thrice weekly episodes of diarrhea or an urgent need to defecate after food ingestion for more than four weeks immediately preceding enrollment.
- •Documented mutation in ATP7A.
- •Must sign and date an Informed Consent Form (ICF).
- •Age ≥ 18 years of age.
- •Ability to adhere to the prescribed oral Northera (Droxidopa) regimen.
- •Willingness to comply with all study visits and procedures.
排除标准
- •Pre-existing liver (e.g., hepatitis, biliary atresia, cirrhosis) or kidney disease (i.e., calculated glomerular filtration rate <30 ml/min).
- •History of hypertension, anti-hypertensive therapy, heart failure (or decreased ejection fraction), cardiac arrhythmia, or bleeding diatheses.
- •Any disease or condition that, in the opinion of the Investigator, has a high probability of precluding the subject from completing the study or where the subject cannot or will not appropriately comply with study requirements.
- •Any alpha-1 adrenoreceptor agonist, beta-blocker, DOPA decarboxylase inhibitor, midodrine, ephedrine, or any triptan medication as a concomitant medication.
研究组 & 干预措施
Placebo (Treatment B)
Empty gelatin color capsules (sky blue and white, size 0) filled with cellulose microcrystalline and physically indistinguishable from Treatment A capsules. Frequency of administration (by mouth) will be twice daily for six weeks
干预措施: Placebo (Other)
Northera™ (Droxidopa) (Treatment A)
Northera (Droxidopa) (Treatment A) will be provided to adult subjects as a capsule with 100mg, 200mg, or 300mg of Northera (Droxidopa) contained within gelatin color capsules (sky blue and white, size 0) based on findings from the dose titration visit. These capsules are physically indistinguishable from the Treatment B (placebo) capsules. Frequency of administration (by mouth) will be twice daily for six weeks.
干预措施: Droxidopa (Drug)
结局指标
主要结局
Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE v5 tool
时间窗: Six week periods of Active drug versus Placebo
Grade 1-5 with increasing severity from 1 to 5
Treatment Related Adverse Events as Assessed by CTCAE v4.0
时间窗: TEAEs in 6 week periods of either active drug (droxidopa) or placebo
Treatment related adverse events as assessed by CTCAE v 4.0 by study arm
次要结局
- Changes in systolic blood pressure after Northera (Droxidopa)(Six week periods of active drug versus placebo)
- Change in plasma catechol levels after Northera (Droxidopa)(Six week periods of active drug versus placebo)
- Changes in Up and Go test performance after Northera (Droxidopa)(Six week periods of active drug versus placebo)
- Changes in gastrointestinal symptoms after Northera (Droxidopa)(Six week periods of active drug versus placebo)
- Changes in Time standing duration after Northera (Droxidopa)(Six week periods of active drug versus placebo)
- Changes in 6 minute walk test performance after Northera (Droxidopa)(Six week periods of active drug versus placebo)
- Mean Change in Systolic Blood Pressure in Tilt Position(Change in systolic BP in tilt position during each 6 week treatment arm (droxidopa and placebo) compared to baseline.)
- Mean Change in Diastolic Blood Pressure in Tilt Position(The change in diastolic BP in tilt position during each 6 week treatment arm (droxidopa and placebo) compared to baseline.)
- Plasma Catechol Levels(Change in plasma catechols between each 6 week treatment arm (droxidopa and placebo))
- Change From Baseline in Daily Bowel Movements(Change from baseline in daily bowel movements per day during each 6 week treatment arm (droxidopa and placebo).)
- Change From Baseline in Time Standing Duration(Change from baseline in standing time duration during each 6 week treatment arm (droxidopa and placebo).)
- Change From Baseline in Timed Up and Go (TUG) Test Performance(Change from baseline in TUG test performance during each 6 week treatment arm (droxidopa and placebo))
- Change From Baseline in 6 Minute Walk Test Performance(Change from baseline in the 6MW distance during each 6 week treatment arm (droxidopa and placebo))
- Change From Baseline in Scores on the Orthostatic Hypotension Symptom Assessment (OHSA) Questionnaire(Change from baseline in OHSA score during each 6 week treatment arm (droxidopa and placebo))
研究者
Stephen G. Kaler, MD
Professor
Nationwide Children's Hospital