Charles Lapp

Charles W. Lapp, MD, is an Internist and Medical Director at Hunter-Hopkins Center in Charlotte, NC with a practice specializing in ME/CFS, FM, and related conditions. Earlier in his career, he practiced family medicine and pediatrics in Raleigh, NC. He became interested in ME/CFS following an outbreak of three small epidemics of a chronic fatiguing illness in the Raleigh area. One of these outbreaks was among all the members of the N.C. Symphony Orchestra.

"Patients started coming to me with persistent flulike symptoms[...]They would work one day and have to sleep for two. Perfectly well-adjusted people became disabled almost overnight.”

From 1992 to 1995 Dr. Lapp acted as Medical Director of the Cheney Clinic in Charlotte, in collaboration with Dr. Paul Cheney. In August 1995, Dr. Lapp opened the Hunter-Hopkins Center. His center does testing for disability insurance such as the 2-day Cardiopulmonary exercise testing (CPET) and a Computer-assisted cognitive function test.

He is currently in practice with Dr. Laura Black.

Awards

• 2009, Nelson Gantz Outstanding Clinician Award awarded to a physician who emulates Nelson Gantz's clinical acumen, his passion for medicine, and his empathy for persons with CFS/FM awarded by IACFS/ME

Pediatric Case Definition

• 2006, "A Pediatric Case Definition for Myalgic Encephalomyelitis and Chronic Fatigue Syndrome"

  "Summary: For a diagnosis of chronic fatigue syndrome (CFS), most researchers use criteria that were developed by Fukuda et al. (1994), with modifications suggested by Reeves et al. (2003). However, this case definition was established for adults rather than children. A Canadian Case Definition (ME/CFS; Myalgic Encephalomyelitis/CFS) has recently been developed, with more specific inclusion criteria (Carruthers et al., 2003). Again, the primary aim of this case definition is to diagnose adult CFS. A significant problem in the literature is the lack of both a pediatric definition of ME/CFS and a reliable instrument to assess it. These deficiencies can lead to criterion variance problems resulting in studies labeling children with a wide variety of symptoms as having ME/CFS. Subsequently, comparisons between articles become more difficult, decreasing the possibility of conducting a meta-analysis. This article presents recommendations developed by the International Association of Chronic Fatigue Syndrome Pediatric Case Definition Working group for a ME/CFS pediatric case definition. It is hoped that this pediatric case definition will lead to more appropriate identification of children and adolescents with ME/CFS."

Clinical Trials

The Hunter-Hopkins Center is currently one of two clinical sites participating in the Hemispherx Biopharma 511/open label Ampligen trials to gain FDA approval. Ampligen is an IV medication given twice weekly in the Hunter-Hopkins infusion room. For more information in this program please see this link: Ampligen study at Hunter-Hopkins.

Clinic location

Hunter-Hopkins Center

7421 Carmel Executive Park Dr.

Charlotte, North Carolina 28226

Telephone: (704) 543-9692

Email: drlapp@drlapp.net

Notable Studies

• 2017, Multi-Site Clinical Assessment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (MCAM): Design and Implementation of a Prospective/Retrospective Rolling Cohort Study

  "Abstract - In the Multi-Site Clinical Assessment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (MCAM), we relied on expert clinician diagnoses to enroll patients from 7 specialty clinics in the United States in order to perform a systematic collection of data on measures of myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS). Healthy persons and those with other illnesses that share some features with ME/CFS were enrolled in comparison groups. The major objectives were to: 1) use standardized questionnaires to measure illness domains of ME/CFS and to evaluate patient heterogeneity overall and between clinics; 2) describe the course of illness, identify the measures that best correlate with meaningful clinical differences, and assess the performances of questionnaires as patient/person-reported outcome measures; 3) describe prescribed medications, orders for laboratory and other tests, and management tools used by expert clinicians to care for persons with ME/CFS; 4) collect biospecimens for future hypothesis testing and for evaluation of morning cortisol profiles; and 5) identify measures that best distinguish persons with ME/CFS from those in the comparison groups and detect subgroups of persons with ME/CFS who may have different underlying causes. Enrollment began in 2012 and is planned to continue in multiple stages through 2017. We present the MCAM methods in detail, along with an initial description of the 471 patients with ME/CFS who were enrolled in stage 1."

• 2016, CDC Grand Rounds: Chronic Fatigue Syndrome — Advancing Research and Clinical Education. Morbidity and Mortality Weekly Report
• 2012, A double-blind, placebo-controlled, randomized, clinical trial of the TLR-3 agonist rintatolimod in severe cases of chronic fatigue syndrome.

  Abstract: "A Phase III prospective, double-blind, randomized, placebo-controlled trial comparing twice weekly IV rintatolimod versus placebo was conducted in 234 subjects with long-standing, debilitating CFS/ME at 12 sites. The primary endpoint was the intra-patient change from baseline at Week 40 in exercise tolerance (ET). Secondary endpoints included concomitant drug usage, the Karnofsky Performance Score (KPS), Activities of Daily Living (ADL), and Vitality Score (SF 36). Subjects receiving rintatolimod for 40 weeks improved intra-patient placebo-adjusted ET 21.3% (p = 0.047) from baseline in an intention-to-treat analysis. Correction for subjects with reduced dosing compliance increased placebo-adjusted ET improvement to 28% (p = 0.022). The improvement observed represents approximately twice the minimum considered medically significant by regulatory agencies. The rintatolimod cohort vs. placebo also reduced dependence on drugs commonly used by patients in an attempt to alleviate the symptoms of CFS/ME (p = 0.048). Placebo subjects crossed-over to receive rintatolimod demonstrated an intra-patient improvement in ET performance at 24 weeks of 39% (p = 0.04). Rintatolimod at 400 mg twice weekly was generally well-tolerated.

• 2007, Defining the Occurrence and Influence of Alpha-Delta Sleep in Chronic Fatigue Syndrome

  "Abstract: BACKGROUND: Patients with chronic fatigue syndrome (CFS) present a disordered sleep pattern and frequently undergo polysomnography to exclude a primary sleep disorder. Such studies have shown reduced sleep efficiency, a reduction of deep sleep, prolonged sleep initiation, and alpha-wave intrusion during deep sleep. Deregulation of the 2-5A synthetase/RNase L antiviral pathway and a potential acquired channelopathy are also found in a subset of CFS patients and could lead to sleep disturbances. This article compiles a large sleep study database on CFS patients and correlates these data with a limited number of immune parameters as it has been thought that RNase L could be associated with these sleep disturbances. METHODS: Forty-eight patients who fulfilled 1994 Centers for Disease Control and Prevention criteria for CFS underwent extensive medical evaluation, routine laboratory testing, and a structured psychiatric interview. Subjects then completed a complaint checklist and a two-night polysomnographic investigation. RNase L analysis was performed by gel electrophoresis using a radiolabeled 2',5'-oligoadenylate trimer. Basic descriptive statistical parameters were calculated. RESULTS: Patients experienced a prolonged sleep latency, showed a low sleep efficiency index, and had a low percentage of slow wave sleep. The present alpha-delta intrusion correlated with anxiety; no correlations appeared, however, between alpha-delta sleep and immunologic parameters, including RNase L. CONCLUSIONS: The main findings are 1) validation of sleep latency problems and other sleep disturbances as already suggested by several authors; 2) alpha-delta intrusion seems associated with anxiety; and 3) elevated RNase L did not correlate with alpha-delta sleep.

• 2006, Recognizing Pediatric CFS in the Primary Care Practice: A Practicing Clinician's Approach

  "Abstract - Pediatricians and primary care physicians may be uncomfortable diagnosing Chronic Fatigue Syndrome in children because a good diagnostic tool has not been available. Deferring a diagnosis, however, may lead to apprehension, over-utilization of medical resources in a search for validity, a delay in treatment, and possibly inappropriate coping techniques. This case-based article discusses symptoms and signs seen in adolescent patients with CFS, evaluation of suspect cases, and both current and future diagnostic case definitions."

• 1999, The Relationship Between Chronic Fatigue Syndrome and Chemical Exposure

  "Summary - Overlapping symptomatologies between chronic fatigue syndrome (CFS) and chemical sensitivity have been observed by different investigators. Interferon-induced proteins 2-5A synthetase and protein kinase RNA (PKR) have been implicated in the viral induction of CFS. The objective of this study was to measure 2-5A and PKR activity in patients with CFS and toxic chemical exposure. Based on the CDC definition and criteria, twenty CFS patients who were positive for viral genome(s) (mainly HHV6; HTLV II, EBV, and CMV) and did not have any history of exposure to toxic chemicals were included in this study. As a comparison, the second group of patients consisted of twenty individuals from the same geographical area who were negative for viral genomes but had been exposed to methyl tertiary-butyl ether concentration of up to 70 ppb and benzene concentration up to 14 ppb. All patients complained of fatigue and other symptoms overlapping between the two groups. From all 40 patients, blood was drawn, leukocyte extract was prepared and assayed for 2-5A synthetase and PKR activity. Clinical specimens which were positive for viral genomes showed from 2.2-38.7 fold increase in 2-5A activity and 1.3-13.5 fold increase in PKR activities over the background of the healthy controls. Similarly, the second group (negative for viral genomes, but exposed to chemicals) showed a 1.1-29.2 fold increase for 2-5A synthetase and a 1.3-11.6 fold increase for PKR when they were compared to healthy subjects. To elucidate mechanisms involved in viral versus chemical induction of 2-5A synthetase and PKR, MDBK cell lines were cultured either in the presence or absence of HHV6, MTBE, or benzene. 2-5A and PKR activities were measured in all the above conditions. A clear induction of 2-5A and PKR was observed when MDBK cells were exposed to HHV6, MTBE, and benzene indicating that induction of interferon-in-duced proteins are not unique to viruses. We conclude that 2-5A and PKR are not only biomarkers for viral induction of CFS, but biomark-ers to other stressors that include MTBE and benzene."

• 1998, Downregulation of RNase L inhibitor correlates with upregulation of interferon-induced proteins (2-5A synthetase and RNase L) in patients with chronic fatigue immune dysfunction syndrome.
• 1997, Management of Chronic Fatigue Syndrome in Children: A Practicing Clinician's Approach

Talks & interviews

• 17 Apr 2017, Dr Charles Lapp - An overview of ME/CFS Diagnosis and Management
• 16 Feb 2016, CDC Grand Rounds - Chronic Fatigue Syndrome: Advancing Research and Clinical Education with Charles Lapp, MD, Elizabeth Unger, PhD, MD, Anthony Komaroff, MD and Avindra Nath, MD

HHS/CFSAC Testimony

• Oct 29, 2009 Testimony (read by Cort Johnson)

Open Letter to The Lancet

Two open letters to the editor of The Lancet urged the editor to commission a fully independent review of the PACE trial, which the journal had published in 2011. In 2016, Dr. Lapp, along with 42 colleagues in the ME/CFS field, signed the second letter.

• 10 February 2016, An open letter to The Lancet, again - Virology blog

Online presence

• PubMed - Charles Lapp
• Hunter-Hopkins Center Facebook page
• Hunter-Hopkins Center website

Learn more

• 2012, What Are The Most Important Things To Remember About CFS/FM?
• Curriculum Vitae - Charles W. Lapp, MD

See also

• NIH Post-Infectious ME/CFS Study
• Ampligen
• 1984 Chapel Hill outbreak
• Dr. Laura Black

cognition Thought processes, including attention, reasoning, and memory.

myalgic encephalomyelitis (M.E.) - A disease often marked by neurological symptoms, but fatigue is sometimes a symptom as well. Some diagnostic criteria distinguish it from chronic fatigue syndrome, while other diagnostic criteria consider it to be a synonym for chronic fatigue syndrome. A defining characteristic of ME is post-exertional malaise (PEM), or post-exertional neuroimmune exhaustion (PENE), which is a notable exacerbation of symptoms brought on by small exertions. PEM can last for days or weeks. Symptoms can include cognitive impairments, muscle pain (myalgia), trouble remaining upright (orthostatic intolerance), sleep abnormalities, and gastro-intestinal impairments, among others. An estimated 25% of those suffering from ME are housebound or bedbound. The World Health Organization (WHO) classifies ME as a neurological disease.

double blinded trial A clinical trial is double blinded if neither the participants nor the researchers know which treatment group they are allocated to until after the results are interpreted. This reduces bias. (Learn more: www.nottingham.ac.uk)

agonist A chemical that binds to the receptor and stimulates it's function, e.g., morphine is an opioid agonist that binds to the opioid receptor, reducing pain. The opposite of an antagonist.

phase three Last phase of clinical trials before a drug can be approved for public use. Whereas Phase one assesses basic safety, and Phase two assesses basic efficacy, Phase three uses many trial participants to fully assess both safety and efficacy, and overall benefit/risk.

Short Form 36-Item Health Survey (SF-36) - A 36-item patient-reported questionnaire, used to determine patient health status and quality of life.

Centers for Disease Control and Prevention (CDC) - The Centers for Disease Control and Prevention is a U.S. government agency dedicated to epidemiology and public health. It operates under the auspices of the Department of Health and Human Services.

Centers for Disease Control and Prevention (CDC) - The Centers for Disease Control and Prevention is a U.S. government agency dedicated to epidemiology and public health. It operates under the auspices of the Department of Health and Human Services.

genome an organism's complete set of DNA, including all of its genes

cytomegalovirus (CMV) - A common herpesvirus found in humans. Like other herpesviruses, it is a life-long infection that remains in a latent state inside the human body, until it is 'reactivated' by appropriate conditions. CMV infects between 60% to 70% of adults in industrialized countries and close to 100% in emerging countries. Much is unknown about this virus, although it has been found in salivary glands and myeloid blood cells such as monocytes. It has also been linked to the development of certain cancers. Congenital CMV is a leading infectious cause of deafness, learning disabilities, and intellectual disability. A common treatment for CMV is valganciclovir, commonly known as Valcyte.

genome an organism's complete set of DNA, including all of its genes

assay 1. (verb) analysis (as of an ore or drug) to determine the presence, absence, or quantity of one or more components. 2. (noun) In biochemistry, any laboratory protocol used to test a sample for one or more qualities.

Chronic Fatigue and Immune Dysfunction Syndrome (CFIDS) - Chronic Fatigue and Immune Dysfunction Syndrome is another term for Chronic Fatigue Syndrome, but one which emphasizes the immunological aspects of the disease. Popular in the 1990s, this term has apparently fallen into disuse.

Chronic Fatigue Syndrome Advisory Committee (CFSAC) - (sometimes pronounced SIF-SACK) A US government advisory council that met twice per year, covering current topics related to Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Meetings usually lasted for two days and the results were presented to the Secretary of Health and Human Services (HHS). After 15 years, on September 5, 2018, CFSAC's charter was not renewed by the Department of HHS, effectively dissolving the committee without notice or warning.