Phase III, Placebo-Controlled, Double-Blind Crossover Study of Slow-Release Methylphenidate (Concerta ™) for Treatment of HIV Associated Neurocognitive Disorder
试验速览
- 阶段
- 3 期
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Change in rate of reaction time as measured by neuropsychological testing
研究概览
简要总结
This study is being done to see if a drug called long acting methylphenidate (Concerta) is safe and effective as a treatment for problems with mental function in adults infected with HIV.
A subset of patients with HIV-associated memory loss have a defect in the speed with which they learn and process information. Methylphenidate drugs, such as Ritalin or Concerta, have been shown on tests to improve the ability to rapidly absorb information; these tests are called "reaction time tests". These drugs are already FDA-approved to treat Attention Deficit Disorders: ADD or ADHD.
At baseline, all subjects get tests of memory and brain function; then they are split into two groups. One group on this study will receive Concerta for 2 weeks, and a second group will receive a placebo x 2 weeks. After that period both groups will receive memory and other tests of brain function, and then the groups will switch. The first group will receive placebo and the second will receive Concerta x 2 weeks, followed by more memory and neurological tests. After that all subjects will have the option to receive Concerta for free for 8 more weeks. At the last visit all subjects get memory and brain tests again.
详细描述
There are 11 study visits in 14 weeks.
In Part I of the study one-half of the subjects will receive ConcertaTM and one-half will receive placebo.
After 2 weeks all subjects will stop their study medication for 2 week (the "washout period"), and then all of the subjects who received placebo will then receive 2 weeks of methylphenidate, and all of the subjects who received long acting methylphenidate will receive placebo for 2 weeks.
The subject will be invited to enter Part II of the study if she/he still qualifies. During this portion of the study, the subject will receive ConcertaTM for 8 weeks. The subject does not have to be on Part II of this study to be on this study.
Screening visit. (4 hours)
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 64 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Men and women 18 years of age or older and less than 65 years of age.
- •Able to read and understand English.
- •HIV infected on stable ART regimen for 5 months or greater, and not likely to change regimen for the duration of the study.
- •Significant dementia but able to give consent (International HIV Dementia Scale score <10).
- •Significant cognitive slowing on screening, defined as 1 SD below normal (t-score >60) on the Conner's CPT-II reaction time test.
- •Beck Depression Inventory score <
- •Documented HIV-1 RNA PCR <50 copies/mL and documented CD4 count >200 within 3 months of entry visit.
- •Baseline CBC and chemistry panel Grade 1 or normal.
- •For females of reproductive potential (women who have not been post-menopausal for at least 24 consecutive months, i.e., who have had menses within 24 months prior to study entry), or women who have not undergone surgical sterilization, specifically hysterectomy or bilateral oophorectomy or tubal ligation) will require a negative serum or urine pregnancy test within 48 hours prior to entry.
- •NOTE: Subject reported history is considered acceptable documentation of hysterectomy, bilateral oophorectomy, tubal ligation, tubal micro-inserts, menopause, and vasectomy/azoospermia.
- •All subjects must agree not to participate in the conception process (e.g., active attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization), and if participating in sexual activity that could lead to pregnancy, the subject/partner must use at least two reliable methods of contraception, (condoms, without a spermicidal agent; a diaphragm or cervical cap without spermicide; an IUD; or hormone-based contraceptive), for 2 weeks before study treatment, while receiving study treatment, and for 6 weeks after receiving study treatment.
- •Ability and willingness of subject to provide informed consent.
排除标准
- •Inability to give informed consent. No proxy consent allowed.
- •Uncontrolled hypertension (SBP >140 and DBP >90 at screening and baseline).
- •Untreated hypogonadism, hypothyroidism or hyperthyroidism.
- •Initiation of antidepressants, thyroid medication or anabolic steroids within 6 weeks of screening visit.
- •Pregnancy or breast feeding.
- •Clinically significant EKG abnormalities at screening.
- •History of coronary artery disease, atherosclerotic disease, left ventricular hypertrophy, cardiomegaly, syncope, congestive heart failure, myocardial infarction, pacemaker, clinically significant arrhythmia, angina, history of treatment for arrhythmia.
- •Brain related opportunistic infections, stroke, intracranial lesions/disease, or meningitis.
- •History of epilepsy.
- •Untreated depression.
- •Uncontrolled diabetes (glucose <70 or >200 at screening).
- •Use of interferon or ribavirin during study and for 1 month prior to screening.
- •History of bipolar disorder, Alzheimer's dementia, ALS, Parkinson's disease or other medical dementias other than HIV-related.
- •History of schizophrenia, mania or other serious mental illness.
- •History of methylphenidate allergy.
- •Other serious concurrent medical illness other than HIV.
- •History of radiation therapy to the brain or brain injury.
- •History of crystal methamphetamine, cocaine, LSD use or other recreational substance use other than marijuana within the 12 months prior to screening and for the duration of the study.
- •Plan to use marijuana or marinol during the entire study duration and one month prior to screening visit.
- •Plan to drink 7 or more alcoholic drinks per week during the 4 weeks prior to screen visit and for the duration of the study.
- •History of alcohol dependence, alcohol abuse, cocaine addiction, crystal methamphetamine addiction or other recreational drug addiction or treatment for addiction or dependence within 5 years of screening visit.
- •If subject is using prescription narcotics, should be on a stable dose for at least 1 month prior to screening and throughout the study.
- •Previous use of Concerta™, Ritalin™, atomexitine or Adderall™ or other psychostimulants (e.g. modafinil, armodafinil) for 3 months prior to screening visit and for duration of the study.
- •History of tic disorders in the past 3 months or any history of Tourette's syndrome.
- •Greater than 10% below ideal body weight (IBW for men = 50 kg + 2.3 kg per inch over 5 feet of height, and IBW for women = 45.5 kg + 2.3 kg per inch over 5 feet of height)
- •Uncontrolled migraine headaches.
- •History of short gut syndrome, Meckel's diverticulum, or cystic fibrosis.
- •Family history of sudden cardiac death in a young relative.
- •History of fainting with exercise.
- •History of attention deficit disorder will be excluded, defined as a score greater than 6 on the Childhood ADHD Symptoms Scale.
研究组 & 干预措施
Group A: 2 tabs of 18 mg Concerta daily
20 subjects to receive active study drug in a blinded fashion x 2 weeks, then washout x 2 weeks, then cross over to receive matched placebo x 2 weeks.
干预措施: Long acting methylphenidate (Drug)
Group B: Matched placebo, 2 tabs daily
Group B to receive matched placebo x 2 weeks, then washout x 2 weeks, then cross over to receive active drug in a blinded fashion x 2 weeks.
干预措施: Matched placebo (Drug)
结局指标
主要结局
Change in rate of reaction time as measured by neuropsychological testing
时间窗: 10 weeks of study drug exposure
The Conner's CPT-II at screening, and at weeks 1, 5, and 14.
次要结局
- Number of Subjects with Adverse Events as Measures of Safety and Tolerability of Concerta in HIV infected adults(10 weeks of drug exposure)
研究者
Ardis Ann Moe, M.D.
Associate Professor of Medicine
University of California, Los Angeles