ACTIVE RESEARCH STUDIES

The research activities of the Division focus on four broad substantive areas which have considerable overlap but have naturally evolved as a result of our previous research findings, as well as the background and expertise of our core faculty. These areas include:

Acupuncture Research
The primary goal of these studies is to develop the appropriate methodology for evaluating this modality in order to evaluate efficacy, safety, and mechanisms of action within the context of a variety of clinical conditions.

Placebo Research
The primary goal for these studies is to develop a research and scholarly agenda concerning placebo effects and controls in research methodology. The research questions focus on all aspects of placebo, including the extent of the effect in any particular disease, whether the effect can be modulated, the components of the placebo response, the basic physiological and psychological mechanisms, and whether or not some individuals repeatedly show a placebo response.

Botanical Research
This is the newest area in which the Division will be focusing, but one which is the closest to the model of the new NIH roadmap in which inter-institutional and cross-disciplinary investigators will work together to facilitate fundamental discovery and translate that knowledge into effective preventive and therapeutic strategies. Our work to date has concentrated on utilizing collaborative local and international partnerships to identify and prioritize promising herbal medicines wich can be systematically procured, extracted, characterized, and subsequently tested in pre-clinical settings. Ultimately, the most successful of these will be tested in multi-site clinical trials.

Health Services Research
The primary aim of these studies is to examine directly the clinical and cost-effectivess of individual or multi-therapy interventions in the treatment of well-defined clinical populations (e.g., adults with low-back pain).

Acupuncture

RO1 AT001414
Acupuncture for Irritable Bowel Syndrome (Kaptchuk)
04/01/03-12/31/06

Little is known about acupuncture's efficacy for Irritable Bowel Syndrome (IBS). This trial uses a manualized acupuncture treatment format that closely follows clinical practice and allows flexibility in designing individualized treatments. In addition, a second parallel qualitative study will follow a subgroup of patients throughout the trial to explore the relationships between patients' interpretations and understandings (what anthropologists call "meaning") of irritable bowel and their response to treatment. Cortisol levels (an important stress hormone) will also be assessed. This will be a 3-arm trial: Active acupuncture, placebo acupuncture, and wait list.

Status: Recruitment initiated.

U19 AT002022
NESA Acupuncture Research Collaborative (Buring)
9/25/03-12/31/06

As a Developmental Center for Research in Complementary and Alternative Medicine (DCRC), this grant brings together leaders from the oriental medicine (OM) and conventional medicine communities to evaluate critically the efficacy and safety of acupuncture, and develop sound methodologies and feasible study designs required for Asian Medicine research. This project strengthens and builds upon ongoing collaborations between the New England School of Acupuncture (NESA), the Harvard Medical School Division and Research Center, and two other HMS-affiliated institutions, the Dana Farber Cancer Institute and Children’s Hospital Boston. The DCRC involves three developmental/exploratory studies (two of which focus on acupuncture for treatment of women’s health issues) and two infrastructure cores (Administrative and Clinical Trials).

Status: Projects initiated. Protocols finalized and IRB applications in progress. Recruitment to begin 6/04.

This project tests a research strategy and protocols for the purchase, extraction, fractionation, and characterization of compounds with potential chemo-therapeutic and chemo-preventive properties. The results from this study will provide pilot data and procedures to be used in an NIH program project or specialized center of research grant (P-50).

Status: Forty-five herbs have been extracted and fractionated and are currently undergoing high throughput bioassay screening within the ICCB at HMS.

The Epilepsy Cure (Fndtn)
Asian Herbs for Epilepsy (Schachter)
3/1/04-2/28/05

The specific aims of this grant are to: 1) systematically procure, extract, and characterize herbal medicines identified as promising for epilepsy; 2) to test these well-characterized herb extractions in validated animal models of epilepsy, and 3) to submit those herb extractions with anti-seizure properties (as demonstrated by the animal studies) to high-throughput screening to evaluate for biological activity.

Status: Testing in completed and analysis is ongoing.

Health Services and Clinical Trials

R21 AT002564
Patient Variables and Placebo Response in IBS (Ablon)
9/01/05-7/31/07

Research on whether patient psychological and personality variables can predict placebo response has been inconclusive and contradictory. Part of the problem in identifying and validating these patient variables arises out of the methods used to assess them. In particular, prior investigations have assessed these variables in isolation from the patient-practitioner relationship, often via self-report personality questionnaires taken at baseline. The approach in this study is unique in that we will study patient variables not in isolation but rather in context, as they manifest themselves during a clinical encounter. We hypothesize that the important patient factors influencing placebo response are not to be found in global measures of personality in general nor in attitude measures collected just prior to treatment, but rather in specific measures of the interpersonal process that occurs between a particular patient and a particular practitioner at a particular point in time.

Status: This study will use data generated in an earlier trial which has just completed recruitment.

R01 AT002454
Tai Chi Mind-Body Therapy for Chronic Heart Failure (Yeh)
9/29/04-6/30/07

This study will examine Tai Chi, a meditative mind-body exercise form that has not yet been rigorously studied in patients with heart failure despite increasing popularity among the general public. Exercise has only recently been recognized as an important component of conventional HF management. Optimal protocols have not yet been defined in this population. Existing clinical trials focus solely on physical exercise that has no mindful component, such as treadmill or bicycle training. Tai Chi, however, may have advantages over conventional exercise forms and be particularly suited to frail, de-conditioned patients. With origins in Chinese healing and martial arts, Tai Chi incorporates both slow, gentle physical activity with meditation, relaxation and self-awareness and can be easily performed by chronically ill individuals with HF.

The primary goal of our proposed research is to determine the potential benefit of a tailored 12-week Tai Chi exercise program on functional capacity and health related quality-of-life in patients with chronic HF. The overarching secondary goal is to begin to understand the mechanisms underlying any beneficial effect of Tai Chi. Through exploration of various physiologic and metabolic pathways and behavioral/ psychosocial indices, we will be in a better position to design future mechanistic studies. In addition, this study will provide necessary data to analyze the cost implications for Tai Chi as adjunctive therapy for HF.

Status: Study has just started recruitment.

R01 AT00905
Model of Integrative Care in an Academic Health Center
(Eisenberg)
9/25/01-6/30/06

The purpose of this application is to develop a replicable model of integrative care within an academic medical center in order to plan subsequent controlled trials. It is intended to serve as a prototype to be refined and replicated at other hospitals regionally and nationally. The four aims of the project include:

1. Development of strategies procedures (i.e. credentialing, liability, pharmacy and therapeutics guidelines, data tracking, billing, administrative requirements) necessary to open an integrative care center within an academic health center.
2. To implement and refine these strategies in the operation of an integrative care clinical facility within an academic health center (BWH);
3. To demonstrate our ability to evaluate the effectiveness of care provided by the Integrative Care Center in a pilot RCT involving subjects with persistent low back pain;
4. To review the results of our pilot study to design a subsequent full-scale trial with adequate statistical power; to summarize the cost of building and sustaining this model; and, to document our strategies and disseminate our procedures, enabling transfer and refinement of the model at other sites.

Status: Policies and procedures have been developed. A hospital partner has been identified (i.e. BWH). The clinician team has been identified and has participated in training over the last eight months. An RCT (n=60) has been designed and approved by the Partner’s IRB and has been initiated.

1R21 CA098487
Massage for Hospitalized Patients with Metastatic Cancer
4/1/04-3/31/06

Symptoms such as pain and nausea are common among patients with metastatic cancer, and symptom control is often inadequate. Massage therapy has been advocated as adjunctive therapy in the management of cancer related pain, but has received little careful study. Our study will enroll 100 patients admitted to the hospital with metastatic cancer and randomize them to receive massage therapy, a sham massage control, or usual care while in the hospital. Following completion of the hospital-based data collection, half of subjects with caregivers will be randomized to receive instruction to enable caregivers to provide massage for patients at home. We will collect data from patients and caregivers to determine the impact of hospital-based massage therapy and home-based caregiver massage on cancer-related symptoms and quality of life.

Status: Study is in recruitment.

Education

T32 AT000051
Research Training: Complementary and Integrative Medicine (Phillips)
9/30/99-7/31/09

In 2003 Harvard Medical School's NIH fellowship training grant for training in integrative medicine was renewed for a second five-year term. Although academic centers devoted to CAM research have been funded, there is a shortage of trained clinical investigators with interest and expertise in CAM modalities. Therefore, NIH-funding training programs are required to prepare trainees for research careers in the field. This program is the first post-doctoral fellowship in CAM research to be based at Harvard MedicalSchool. The program has graduated sex MD Fellows to date, all of whom have moved on to research positions at academic centers or positions combining clinical and research training.

K23 AT002624
BioMind-Body Exercise in the Management of Cardiac Disease (Yeh)
2/01/05-1/31/10

This career development award Dr. Yeh in acquiring additional research skills and experience under the mentorship of nationally and internationally known researchers in a supportive academic environment. Collectively, the three related projects in this proposal will allow her to further focus her research efforts on cardiovascular disease and complementary therapies.

K23 AT003238
Biophysics of Acupuncture: Electrical Properties of Loose CT (Ahn)
9/30/05-9/29/10

This career development proposal supports a long-term inquiry in the biophysical nature of acupuncture meridians and points. This proposal is driven by the hypothesis that electrical signals through loose connective tissue are responsible for communications occurring in the acupuncture network. Recent studies have shown that acupuncture meridians correspond to connective tissue planes. While the anatomical correlation has been made, the physiological significance of this association is unclear. Elucidating the mechanisms underlying these properties may greatly enhance our understanding of acupuncture’s clinical effects.

Completed Studies

RO1 AT00622
Physical CAM Therapies for Chronic Low Back Pain
(Eisenberg)
9/1/00-6/30/04

This study evaluates the relative effectiveness and costs of the three most commonly used physical CAM therapies (acupuncture, chiropractic, and massage) for both older and younger adults with chronic low back pain. Phase I involved testing and refining the components of a randomized clinical trial evaluating acupuncture, chiropractic and massage for chronic low back pain including specification of treatment and comparison groups, subject selection criteria, recruitment and retention strategies, and development of instruments for measuring outcomes. During Phase II, a pilot study, using the findings from Phase I, was conducted to evaluate the three physical CAM treatments. Results of the pilot study will be used to identify unanticipated problems and to estimate the sample sizes required for an adequately powered full-scale trial.

Status: Study complete. Analysis is ongoing.

RO1 AT00607
Optimizing Therapeutic Ratios for Herbs (Goldman)
9/1/00-6/30/05

The goal of this proposal is to investigate whether ginkgo may interact with such prescribed anticoagulants as warfarin and ticlopidine at the level of the cytochrome P450 system. Additional studies will determine which fractions of ginkgo are responsible for its anti-platelet effects and how these fractions relate to ginkgo’s non-specific antioxidant effects, which many believe are responsible for ginkgo’s benefits. By addressing the issues of herbal product consistency and using laboratory models to define chemical and biological mechanisms of potential clinical significance, this proposal offers a paradigm for the multidisciplinary study of commonly used herbal products.

Status: This project is completed and papers are now being authored.

R21 AT001979-01
US-China-Japan Research Consortium on Herbal Medicines
(Eisenberg)
09/25/03 - 03/31/05

This planning grant has the long-term goal of developing an International Center for CAM Research focused on the systematic evaluation of East Asian herbal medicines.

Status: Regular conference calls are held among consortium members to: 1) prioritize top candidate herbs; 2) develop/refine existing protocols to Perform Bioassays/HST evaluations; 3) plan for the Phase II grant submission and clinical trial development.

RO1 AT001414
Usual Care Vs Choice of Alternative Rx: Low Back Pain (Eisenberg)
9/30/99-8/31/03

This study compares two approaches to the management of acute low back pain: usual care (standard benefit) vs. the choice of: usual care, chiropractic, acupuncture or massage therapy (expanded benefit). The results of this randomized trial of 44 subjects will provide valuable information to clinicians, patients and third party payers on the relative benefits and costs of an "expanded benefits" treatment option which incorporates chiropractic, acupuncture and massage services for low back pain.

Status: Study complete. Analysis is ongoing.

G13 LM07575 (NLM)
Legal and Social Barriers to Alternative Medicine
(Cohen)
1/15/02-12/31/04

The project will result in a scholarly, book-length manuscript that critically evaluates the integration of complementary and alternative medical (“CAM”) therapies into conventional medical settings in the United States. Methods have included a critical review of literature and interviews with key personnel in existing, integrated health care centers, regarding the development of their practices and the problems they have encountered. Such a study aims to fill a gap in the current health care literature by collecting the kind of information needed to develop, sustain and evaluate critically the evidence-based clinical integration of CAM therapies in conventional medical settings.

Status: Interviews completed. Draft book manuscript in process.

RO1 AT00402
Sham Device, Pill Placebo Or Treatment For Arm Pain (Kaptchuk)
09/01/00-06/30/04
Status: Recruitment and data collection completed. Analysis is ongoing. A draft manuscript has been submitted.