Methylphenidate for Cancer-Related Fatigue: A Pilot N-of-1 Study
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 3
- 试验地点
- 2
- 主要终点
- Completion Rate of Two Treatment Pairs Using the N-1-T Design
研究概览
简要总结
The overall aim of this pilot study is to conduct a combined N-of-1 trial (N-1-T) of MPH (methylphenidate) for amelioration of fatigue in children with cancer, and to evaluate the N-1-T design both for individual clinical decision making and for clinical trials in symptom management in pediatric oncology patients. Because no one knows which of the study options are best, participants will receive liquid MPH on some days and a placebo on other days. We will compare how the participant feels on MPH days with how they feel on placebo days to determine whether MPH makes a difference.
详细描述
I. To assess the N-1-T as a study design to evaluate a symptom-directed intervention in children with cancer
Primary objective
-To evaluate the feasibility of conducting an N-1-T to evaluate MPH for cancer-related fatigue in children as a group
Secondary objectives
- To evaluate the ability of the N-1-T to assess efficacy of MPH for an individual subject statistically and clinically definite answer (regarding the ability of MPH to reduce fatigue)
- To explore subject/family and oncologist perspectives on N1T participation
- To examine in a preliminary fashion whether there are patient, family, disease or study-related factors that are associated with attrition to help guide future large-scale N1Ts
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 7 Years 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants must be receiving cancer-directed treatment at Dana-Farber Cancer Institute/Children's Hospital Boston or have advanced cancer
- •7-21 years old
- •Laboratory values as outlined in the protocol
- •Negative pregnancy test (for females of childbearing potential only)
- •Child and at least one parent/legal guardian has spoken and written knowledge of English
- •Participant has approximately age-appropriate knowledge of English and is able to understand and complete the single-item Likert scale for rating fatigue
- •Baseline pedsFACIT-F score of 20 or greater
- •Able to reliably take a liquid enterally
- •Physical examination including measurement of pulse and blood pressure conducted within the past 14 days
- •If the child is on an opioid analgesic, the primary oncologist does not anticipate a need to increase opioid during the study
- •Opioid dose stable for at least 5 days immediately prior to enrollment
- •No initiation of or change in the dose of benzodiazepine or other sedative/hypnotic drug in the week prior to enrollment and no forseeable initiation or change during the study
- •If currently on an SSRI, SNRI, or tricyclic antidepressant, on a stable dose of the past week
- •Participant has telephone access for communication with the study team regarding potential dose adjustments and can provide telephone number and alterative phone number
排除标准
- •Participant is regarded by primary oncologist to be at a high likelihood of death within 30 days
- •Diagnosis of brain tumor, metastatic disease to the brain, or current active CNS leukemia
- •Known history of glaucoma
- •Receiving palliative sedation
- •Receipt of MPH or any other psychostimulant, alpha-adrenergic medications, neuroleptics, lithium, monoamine oxidase inhibitors, procarbazine or coumadin in the 14 days prior to enrollment
- •Significant GI disturbance that would impair absorption of the drug
- •History of alcohol or substance abuse in the subject. Subjects living with a household member with a history of alcohol or substance abuse may be excluded if the investigator feels there is a risk of the study medication being abused or diverted
- •Documented history of psychotic or bipolar disorder, delirium, major depression, suicidal ideation, aggressive behavior necessitating psychiatric care, or any other psychiatric condition requiring urgent psychiatric evaluation or immediate initiation of pharmacotherapy
- •History of tics or Tourette's syndrome
- •Prior history of adverse reaction to MPH
- •Uncontrolled hypertension
- •Cardiomyopathy, serious structural cardiac abnormalities, or history of any of the following: ventricular arrhythmia, myocardial infarction, rheumatic fever, spontaneous or unexplained syncope, exercise-induced syncope, or exercise-induced chest pain.
- •Family history of ventricular arrhythmia, a sudden or unexplained event requiring resuscitation or sudden death under age 30 years, known cardiac arrhythmia, hypertrophic cardiomyopathy, or dilated cardiomyopathy.
- •Concurrent participation in a study that prohibits enrollment on any other trials involving cancer-directed or symptom-directed therapies, without approval from the study PI
- •Prior or current medical condition that, in the opinion of the PI, could be exacerbated by MPH
- •Pregnant or breastfeeding women
- •HIV-positive individuals on combination antiretroviral therapy
- •Treatment of fatigue medications or herbal supplements for fatigue during the 14 days prior to enrollment
研究组 & 干预措施
M-P, P-M, M-P
Participants were randomized to receive 3 treatment pairs of placebo (P) then methylphenidate (M) or M then P. Each M or P was given daily for 3 days and therefore treatment duration was 18 days over 3 treatment pairs. M or P was administered orally at a starting dose of 0.3 mg/kg/dose. For participants > 40 kg, the maximum of dose in the first treatment pair was 12.5 mg per dose. Dose escalation to maximum 0.5 mg/kg/dose was permitted.
干预措施: methylphenidate (Drug)
M-P, P-M, M-P
Participants were randomized to receive 3 treatment pairs of placebo (P) then methylphenidate (M) or M then P. Each M or P was given daily for 3 days and therefore treatment duration was 18 days over 3 treatment pairs. M or P was administered orally at a starting dose of 0.3 mg/kg/dose. For participants > 40 kg, the maximum of dose in the first treatment pair was 12.5 mg per dose. Dose escalation to maximum 0.5 mg/kg/dose was permitted.
干预措施: Placebo (Other)
P-M, P-M, M-P
Participants were randomized to receive 3 treatment pairs of placebo (P) then methylphenidate (M) or M then P. Each M or P was given daily for 3 days and therefore treatment duration was 18 days over 3 treatment pairs. M or P was administered orally at a starting dose of 0.3 mg/kg/dose. For participants > 40 kg, the maximum of dose in the first treatment pair was 12.5 mg per dose. Dose escalation to maximum 0.5 mg/kg/dose was permitted.
干预措施: methylphenidate (Drug)
P-M, P-M, M-P
Participants were randomized to receive 3 treatment pairs of placebo (P) then methylphenidate (M) or M then P. Each M or P was given daily for 3 days and therefore treatment duration was 18 days over 3 treatment pairs. M or P was administered orally at a starting dose of 0.3 mg/kg/dose. For participants > 40 kg, the maximum of dose in the first treatment pair was 12.5 mg per dose. Dose escalation to maximum 0.5 mg/kg/dose was permitted.
干预措施: Placebo (Other)
P-M, M-P, M-P
Participants were randomized to receive 3 treatment pairs of placebo (P) then methylphenidate (M) or M then P. Each M or P was given daily for 3 days and therefore treatment duration was 18 days over 3 treatment pairs. M or P was administered orally at a starting dose of 0.3 mg/kg/dose. For participants > 40 kg, the maximum of dose in the first treatment pair was 12.5 mg per dose. Dose escalation to maximum 0.5 mg/kg/dose was permitted.
干预措施: methylphenidate (Drug)
P-M, M-P, M-P
Participants were randomized to receive 3 treatment pairs of placebo (P) then methylphenidate (M) or M then P. Each M or P was given daily for 3 days and therefore treatment duration was 18 days over 3 treatment pairs. M or P was administered orally at a starting dose of 0.3 mg/kg/dose. For participants > 40 kg, the maximum of dose in the first treatment pair was 12.5 mg per dose. Dose escalation to maximum 0.5 mg/kg/dose was permitted.
干预措施: Placebo (Other)
M-P, M-P, M-P
Participants were randomized to receive 3 treatment pairs of placebo (P) then methylphenidate (M) or M then P. Each M or P was given daily for 3 days and therefore treatment duration was 18 days over 3 treatment pairs. M or P was administered orally at a starting dose of 0.3 mg/kg/dose. For participants > 40 kg, the maximum of dose in the first treatment pair was 12.5 mg per dose. Dose escalation to maximum 0.5 mg/kg/dose was permitted.
干预措施: methylphenidate (Drug)
M-P, M-P, M-P
Participants were randomized to receive 3 treatment pairs of placebo (P) then methylphenidate (M) or M then P. Each M or P was given daily for 3 days and therefore treatment duration was 18 days over 3 treatment pairs. M or P was administered orally at a starting dose of 0.3 mg/kg/dose. For participants > 40 kg, the maximum of dose in the first treatment pair was 12.5 mg per dose. Dose escalation to maximum 0.5 mg/kg/dose was permitted.
干预措施: Placebo (Other)
M-P, P-M, P-M
Participants were randomized to receive 3 treatment pairs of placebo (P) then methylphenidate (M) or M then P. Each M or P was given daily for 3 days and therefore treatment duration was 18 days over 3 treatment pairs. M or P was administered orally at a starting dose of 0.3 mg/kg/dose. For participants > 40 kg, the maximum of dose in the first treatment pair was 12.5 mg per dose. Dose escalation to maximum 0.5 mg/kg/dose was permitted.
干预措施: methylphenidate (Drug)
M-P, P-M, P-M
Participants were randomized to receive 3 treatment pairs of placebo (P) then methylphenidate (M) or M then P. Each M or P was given daily for 3 days and therefore treatment duration was 18 days over 3 treatment pairs. M or P was administered orally at a starting dose of 0.3 mg/kg/dose. For participants > 40 kg, the maximum of dose in the first treatment pair was 12.5 mg per dose. Dose escalation to maximum 0.5 mg/kg/dose was permitted.
干预措施: Placebo (Other)
M-P, M-P, P-M
Participants were randomized to receive 3 treatment pairs of placebo (P) then methylphenidate (M) or M then P. Each M or P was given daily for 3 days and therefore treatment duration was 18 days over 3 treatment pairs. M or P was administered orally at a starting dose of 0.3 mg/kg/dose. For participants > 40 kg, the maximum of dose in the first treatment pair was 12.5 mg per dose. Dose escalation to maximum 0.5 mg/kg/dose was permitted.
干预措施: methylphenidate (Drug)
M-P, M-P, P-M
Participants were randomized to receive 3 treatment pairs of placebo (P) then methylphenidate (M) or M then P. Each M or P was given daily for 3 days and therefore treatment duration was 18 days over 3 treatment pairs. M or P was administered orally at a starting dose of 0.3 mg/kg/dose. For participants > 40 kg, the maximum of dose in the first treatment pair was 12.5 mg per dose. Dose escalation to maximum 0.5 mg/kg/dose was permitted.
干预措施: Placebo (Other)
P-M, P-M, P-M
Participants were randomized to receive 3 treatment pairs of placebo (P) then methylphenidate (M) or M then P. Each M or P was given daily for 3 days and therefore treatment duration was 18 days over 3 treatment pairs. M or P was administered orally at a starting dose of 0.3 mg/kg/dose. For participants > 40 kg, the maximum of dose in the first treatment pair was 12.5 mg per dose. Dose escalation to maximum 0.5 mg/kg/dose was permitted.
干预措施: methylphenidate (Drug)
P-M, P-M, P-M
Participants were randomized to receive 3 treatment pairs of placebo (P) then methylphenidate (M) or M then P. Each M or P was given daily for 3 days and therefore treatment duration was 18 days over 3 treatment pairs. M or P was administered orally at a starting dose of 0.3 mg/kg/dose. For participants > 40 kg, the maximum of dose in the first treatment pair was 12.5 mg per dose. Dose escalation to maximum 0.5 mg/kg/dose was permitted.
干预措施: Placebo (Other)
P-M, M-P, P-M
Participants were randomized to receive 3 treatment pairs of placebo (P) then methylphenidate (M) or M then P. Each M or P was given daily for 3 days and therefore treatment duration was 18 days over 3 treatment pairs. M or P was administered orally at a starting dose of 0.3 mg/kg/dose. For participants > 40 kg, the maximum of dose in the first treatment pair was 12.5 mg per dose. Dose escalation to maximum 0.5 mg/kg/dose was permitted.
干预措施: methylphenidate (Drug)
P-M, M-P, P-M
Participants were randomized to receive 3 treatment pairs of placebo (P) then methylphenidate (M) or M then P. Each M or P was given daily for 3 days and therefore treatment duration was 18 days over 3 treatment pairs. M or P was administered orally at a starting dose of 0.3 mg/kg/dose. For participants > 40 kg, the maximum of dose in the first treatment pair was 12.5 mg per dose. Dose escalation to maximum 0.5 mg/kg/dose was permitted.
干预措施: Placebo (Other)
结局指标
主要结局
Completion Rate of Two Treatment Pairs Using the N-1-T Design
时间窗: 18 days
The feasibility of conducting an N-1-T to evaluate MPH for cancer-related fatigue will be determined by the completion rate of two MPH-placebo pairs.
次要结局
- Rate of Receiving Clinically Definite Answer Regarding the Ability of Experimental Treatment to Reduce Fatigue Using the N-1-T Design(18 days)
- Change Over Treatment Pairs in pedsFACIT-F Score(The pedsFACIT-Fwas administered at baseline and at the end of each treatment pair (TP) and related change in score was calculated for each period: baseline to end of TP 1 (day 6); end of TP 1 to end of TP 2 (day 12); end of TP 2 to end of TP 3 (day 18).)
研究者
Christina K. Ullrich, MD, MPH
Christina Ullrich, MD, MPH
Dana-Farber Cancer Institute