Phase II Multicenter 16-Week Randomized Double Blind Placebo-Controlled Evaluation of the Efficacy, Tolerability and Safety of Memantine Hydrochloride on Enhancing the Cognitive Abilities of Adolescents and Young Adults With Down Syndrome
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 160
- 试验地点
- 2
- 主要终点
- Efficacy of the Drug Memantine as Assessed by Change in Score on the California Verbal Learning Test-II (CVLT-II) Short Form Total Free Recall
研究概览
简要总结
The purpose of this research study is to learn if the medication Memantine Hydrochloride (the study medication) can help adolescents and young adults with Down syndrome. Dr. Alberto Costa and his research team want to see if a 16-week treatment with this medication can improve the participant's ability to learn and remember things. In this study, memantine hydrochloride will be used. Thus, the researchers want to learn whether the study drug can help improve memory in young adults with Down syndrome. To test the effect of the study medicine, half of the people in the study will receive the study medicine and half will receive a placebo (an inactive substance). Memantine is an approved medication to treat memory and thinking problems in persons with Alzheimer disease. However, little is known about the effect of this medication in persons with Down syndrome and it has not been approved for use in persons with Down syndrome.
详细描述
This study seeks to investigate if the medication Memantine Hydrochloride can help young adults with Down syndrome. Two hundred persons with Down syndrome from both genders and between 15 and 32 years of age will be recruited from two sites: Cleveland, OH, USA and São Paulo, SP, Brazil. Participants will be assigned randomly to either a placebo group or a group taking the active medication with a 50% probability of being on either group. Neither the participants nor the investigators will know who will be taking the study medication and who will be taking the placebo during the study. Only the investigational pharmacist will have access to this information.
Up to 60 people with Down syndrome of the recruited study participants will take part on an optional magnetic resonance imaging (MRI) study. This investigation is aimed at helping to make the EEG study more precise and to find out whether the study medication has any significant effect on the structure of the brain.
Additionally, we will recruit a control group of 60 age- and gender-matched participants without Down syndrome. The goal is to investigate how different groups of people activate their brains when they hear or see something, and if he can use high-density EEG and MRI to see how this study medication works in persons with Down syndrome. In other words, this additional control group should help us ascertain which parts of the test results are due to a person having Down syndrome and which ones are not. Persons without Down syndrome will only come for one EEG visit and one MRI visit, and not be asked to take the study medication.
The visits for the participants with Down syndrome will be as follows:
Screening visit (approximately 2-hour long). The subject will be asked about his/her health, medical history, social background, and work background, as well as some simple questions to determine performance on tests of memory and function that are part of this study. Informed consent and assent will be obtained in this visit. At the end of this visit, an EEG machine will be used to access brain responses to different auditory and visual stimuli. Some will be asked if they would be willing to have an MRI performed, but this portion is not imperative.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 15 Years 至 32 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Cytogenetically documented Trisomy 21 or Complete Unbalanced Translocation of Chromosome
- •Mosaic Trisomy 21 and partial translocations will be excluded from the study
- •No pregnancy by serum testing at screening. Females of child-bearing potential, sexually active must be practicing a reliable method of birth control. Urine pregnancy tests will be done at the 2 follow-up medical visits
- •Laboratory findings within normal limits or judged clinically insignificant at baseline
- •Vital signs within normal limits for age. Stable, medically treated hypotension will be allowed
- •ECG must demonstrate predominately normal sinus rhythm. Minor abnormalities documented as clinically insignificant will be allowed
- •Participants and their authorized representatives will provide written informed consent
- •Participants who have received any experimental drug for Down syndrome must undergo a washout
- •All participants must: Be in general good health as judged by the investigators; Be able to swallow oral medication; Have a reliable caregiver or family member who agrees to accompany participant to all visits, provide information about the participant as required by the protocol, and ensure compliance with the medication schedule; Be sufficiently proficient in English (USA) or Portuguese (Brazil) to reliably complete the study assessments
- •Age and gender matching participants without Down syndrome, must be: Males or females without Down syndrome aged-matching (within 3 years) participants with Down syndrome whom they are expected to serve as controls
排除标准
- •Participant weighing less than 40 kg
- •Current psychiatric or neurologic diagnosis other than Down syndrome (e.g., major depressive disorder, schizophrenia, bipolar disorder, autism, Alzheimer disease)
- •Current treatment with psychotropic drugs
- •Drug or alcohol abuse or dependence
- •Significant suicide risk or who would require treatment with electro-convulsive therapy or with psychotropic drugs during the study or who have received treatment with a depot neuroleptic drug within 6 months of entering the study.
- •Current or expected (within the next 6 months) hospitalization or residence in a skilled nursing facility (may reside in group homes or other residential settings with no skilled nursing)
- •Active or clinically significant conditions affecting absorption, distribution, or metabolism of study drug (e.g. inflammatory bowel disease or celiac disease)
- •Significant allergies to or other significant intolerance of memantine therapy, its ingredients, or with contraindications to memantine therapy as stated in the prescribing information
- •Participants who are expected to require general anesthetics during the course of the study
- •Presence or recent history of seizure disorder (< 3 years).
- •Clinically significant and/or clinically unstable systemic disease. (Those with controlled hypothyroidism must be on a stable dose of medication for at least 3 months prior to screening and have normal serum T-4 and TSH at screening; and those with controlled diabetes mellitus must have an HbA1c of < 8.0% and a random serum glucose value of < 170 mg/dl)
- •Severe infections or a major surgical operation within 3 months prior to screening
- •History of persistent cognitive deficits immediately following head trauma.
- •Donation of blood or blood products less that 30 days prior to screening, while participating in the study, or four weeks after completion of the study
- •Inability to comply with the protocol or perform the outcomes measures due to significant hearing or visual impairment or other issues judged relevant by the investigators
- •Exclusion criteria for controls without Down syndrome: History of substance abuse, major psychiatric disorder, attention deficit disorder, or learning disability; Beck Depression Score greater than 10; Exclusion criteria specific to MR scanning; Pregnancy; Neurologic history
研究组 & 干预措施
Placebo
Identically-looking placebo pills to memantine will be dispensed in a 66-day supply (56 days plus 10 extra days) by the study coordinator to participants receiving the placebo at the end of visits 2 and 3.
干预措施: Placebo (Drug)
Memantine
Memantine will be dispensed in a 66-day supply (56 days plus 10 extra days) by the study coordinator to participants receiving the placebo at the end of visits 2 and 3.
干预措施: Memantine (Drug)
结局指标
主要结局
Efficacy of the Drug Memantine as Assessed by Change in Score on the California Verbal Learning Test-II (CVLT-II) Short Form Total Free Recall
时间窗: baseline and 16 weeks from start of treatment
The primary efficacy measure is focused on episodic memory. The CVLT-II short form assesses supraspan word learning ability as an index of episodic verbal long-term memory. We hypothesize that treatment with memantine will produce significant improvements in this test. The main dependent variable selected, based on prior literature was the total number of target items correct summed across learning trials 1-4. The values for this measure have been recorded as change in score from baseline (T1) to after the treatment (T2). Scale Range: from 0 to 36; higher scores represent better outcomes.
次要结局
- Efficacy of the Drug Memantine as Assessed by Change in Score on the Pattern Recognition Memory (PRM; Part of the Cambridge Neuropsychological Test Automated Battery -- CANTAB)(baseline and 16 weeks from start of treatment)
- Efficacy of the Drug Memantine as Assessed by Change in Score on the Paired Associates Learning (PAL) From the Cambridge Neuropsychological Test Automated Battery (CANTAB)(baseline and 16 weeks from start of treatment)
- Efficacy of the Drug Memantine as Assessed by Change in Score on the Recall of Digits Forward (From the Differential Ability Scales; DAS-II)(baseline and 16 weeks from start of treatment)
- Efficacy of the Drug Memantine as Assessed by Change in Score on the Spatial Span (Part of the Cambridge Neuropsychological Test Automated Battery -- CANTAB)(baseline and 16 weeks from start of treatment)
- Efficacy of the Drug Memantine as Assessed by Change in Score on the Spatial Working Memory (Part of the Cambridge Neuropsychological Test Automated Battery -- CANTAB)(baseline and 16 weeks from start of treatment)
- Efficacy of the Drug Memantine as Assessed by Change in Score on the The Go - No Go Task(baseline and 16 weeks from start of treatment)
- Safety and Tolerability of the Drug Memantine as Assessed by Change in QTc Interval(baseline and 16 weeks from start of treatment)