Dr. Haertling was recruited to our training program largely due to her interest in a career as a physician-scientist targeting the improvement in the quality of life of children with oncologic and hematologic disorders. Dr. Haertling’s training provides an excellent platform on which to build a solid research career. She completed her Doctor of Osteopathic Medicine at A.T. Still University in Kirksville, Missouri and her pediatric residency at Saint Louis University’s Cardinal Glennon Children’s Medical Center in St. Louis. While in her residency, she participated in a quality improvement project focused on the effectiveness of pain management of hospitalized patients before and after the institution of a standardized admission protocol. This experience combined with the additional clinical training she received as a first year fellow at Children’s Memorial has allowed her to refine her skills and interest in the development of assessment tools to further evaluate parameters which impact the quality of life of pediatric cancer patients.

During the next two years Dr. Haertling will pursue a hypothesis driven clinical research project under the mentorship of Stewart Goldman, MD, Medical Director of Neuro-oncology, and a committee of three faculty members. Dr. Haertling’s research project will look at the issue of fatigue, a problem that impacts the quality of life of many pediatric cancer patients, but has not been widely studied. As such, there is a critical need to examine a way to minimize the fatigue and other problems associated with cancer and its treatment that many children experience. Such research can lead to improved risk-based care specific to each individual’s cancer diagnosis and treatment. Dr. Haertling will compliment her research activities by enrolling in the Master of Science in Clinical Investigation (MSCI) at Northwestern University.

Fatigue during and after treatment is one of the most prevalent symptoms reported by cancer patients of all ages. Cancer-related fatigue may be acute, or chronic, and is correlated with health status, emotional functioning (depression, anxiety), pain, and cognitive functioning. Fatigue is reported by pediatric cancer patients to be the most distressing symptom they experience from diagnosis to the end of treatment. However, fatigue and the management of fatigue in pediatric cancer patients has not been as well studied as in adult cancer patients. In general, the origin of fatigue in cancer patients is not well understood and is thought to be due to multiple factors. The disease process, radiation and chemotherapy agents, anemia and cachexia (physical wasting caused by disease), psychological conditions, sleep disorders, and nutritional, endocrine and metabolic abnormalities are all considered to be contributing factors.

Carnitine deficiency has been identified in multiple studies of adult cancer patients to be linked to fatigue. Carnitine is a nutrient that helps the body turn fat into energy. Carnitine also has important detoxification functions. It is absorbed from dietary sources, produced endogenously and excreted primarily by the kidneys. It is presumed that patients with carnitine deficiency are susceptible to the development of chronic fatigue.

Carnitine deficiency has been found to occur in 76 to 83 percent of adult cancer patients. In recent studies, most of the adult cancer patients who received levocarnitine (L-carnitine) supplementation were found to have improved fatigue, mood and sleep. In addition, carnitine supplementation has been studied in pediatric patients with metabolic disorders and other chronic illnesses. Its use in pediatric renal patients has been found to be tolerated.

In previous studies of pediatric patients with leukemia a significant decline in total and free carnitine levels was seen between the time of diagnosis and one year after initiation of chemotherapy. After the first year, a gradual recovery of carnitine levels was observed. Despite these findings, no studies have evaluated L-carnitine supplementation for management of fatigue in pediatric cancer patients with carnitine deficiency. Dr. Haertling and her colleagues hypothesize that L-carnitine supplementation in pediatric cancer patients may improve quality of life by decreasing fatigue.

Specific aims of the proposed research:

Primary Aim: Determine the efficacy of L-carnitine supplementation on fatigue in pediatric patients with cancer and carnitine deficiency.

Secondary Aims:

• Further identify the incidence of fatigue in the pediatric cancer population.

• Determine the prevalence of carnitine deficiency in pediatric oncology patients who are receiving treatment and those who have completed therapy.

• Explore the effect of L-carnitine supplementation on performance status and function in patients with pediatric cancer and carnitine deficiency.

• Explore the relationship of carnitine deficiency and fatigue and other selected variables (i.e. anemia, weight/BMI, psychiatric diagnosis, hospitalizations and infections, school attendance).

• Determine the safety and tolerability of L-carnitine supplementation on patients with pediatric cancer.



Explanation of experimental design and methods:

Patients, ages 8 to 18 years, with pediatric oncologic diagnoses who are being treated at Children’s Memorial Hospital will be recruited to participate in this study. Those experiencing carnitine deficiency and with moderate to severe fatigue will be among the patients targeted for this study.

At the baseline visit, an oncology practitioner will take a medical history, perform a physical exam, measure the patient’s height and weight to determine BMI, and obtain blood samples for plasma total and free carnitine and complete blood count. The patient will complete the self-report instruments, developed in part by Dr. Goldman, and his or her performance status will be recorded.

Patients who meet eligibility criteria will be randomized to one of two treatment arms: Patients in Arm A will receive oral L-carnitine twice daily for weeks one through four, while patients in Arm B will receive an oral placebo twice daily for weeks one through four. After week four, all patients will receive oral L-carnitine twice daily for weeks five through eight. Patients will then be allowed to continue or discontinue L-carnitine supplementation after discussion with their physician and will be followed for an additional eighteen weeks. The total duration of the study will be twenty-six weeks.

Free and total carnitine levels and hemoglobin levels will be obtained every two weeks during treatment. Weight, height and BMI will be obtained at two-week intervals during treatment. Performance scores will be determined, the self-report instrument will be completed and a question regarding number of days of school attended will be answered at two-week intervals.

Anticipated results and potential clinical relevance:

Dr. Haertling hypothesizes that this study will provide evidence for the usage of levocarnitine in the management of fatigue in pediatric oncology patients. This study will add to the limited information known about fatigue, which is a significant issue for pediatric cancer patients. Further data regarding carnitine deficiency in this population will be collected and presented.