Pilot Study Comparing Hypnotherapy and Gabapentin for Hot Flashes.
Keywords
Abstract
Description
Roughly half of women diagnosed with pre-menopausal breast cancer will have hormone receptor-positive tumors, which will make them candidates for anti-estrogen therapies. Both endocrine therapy and ovarian ablation have also been shown to improve outcomes in this population.
Hot flashes are a frequent side effect in women receiving anti-estrogen therapy for breast cancer, and have been shown to have a significant impact on patients' quality of life. For example, it has been reported that hot flashes in breast cancer survivors are more severe and result in a more significant impact on quality of life measures when compared with healthy women.
Hormone replacement, the gold standard for the treatment of hot flashes in postmenopausal women, is contraindicated in this population. Non-hormonal drug therapies have been explored for the treatment of hot flashes in this population of women with moderate results. In randomized controlled trials, venlafaxine has been shown to reduce self-reported hot flashes in patients with breast cancer by 25-61%. However, selective serotonin re-uptake inhibitors (SSRIs) and selective norepinephrine re-uptake inhibitors (SNRIs) may interfere with the metabolism of tamoxifen, a common treatment for estrogen-receptor positive breast cancers, by inhibiting the cytochrome P450 2D6 (CYP2D6) enzyme. Gabapentin is a gamma-aminobutyric acid (GABA) analogue commonly used for the treatment of seizure disorders and neuropathic pain. There is some evidence to demonstrate its efficacy in hot flashes to be equivalent to estrogen and superior to antidepressants in postmenopausal women.
In a pilot study of 22 women with breast cancer on tamoxifen, the use of gabapentin for four weeks reduced the frequency of hot flashes by 44.2%, and decreased the hot flash severity scores by 52.6%. These results were confirmed in a larger study of 420 breast cancer survivors who were randomized to receive gabapentin 300mg/d, gabapentin 900mg/d, or placebo. The 900mg/d dose of gabapentin was the most effective; decreasing the frequency of hot flashes by 49% at four weeks. In the group receiving 900mg of gabapentin daily, there was a 12% withdrawal rate at 4 weeks, and 17% at 8 weeks, owing to side effects and subjective inefficacy.
Hypnosis or hypnotherapy, defined as the induction of a deeply relaxed condition that allows the patient to suspend critical faculties and allow suggestibility, has been shown to be effective in not only reducing the daily frequency of hot flashes (by 59%), but also in improving quality of life variables such as insomnia in patients with breast cancer. However, this therapy has never been compared directly to pharmacotherapy in the treatment of therapy-induced hot flashes in patients with breast cancer.
In response to the NCI's 2006 initiatives to expand the goals of clinical trials and include symptom management studies, we are interested in evaluating the role of complementary and alternative therapies for improvement of symptoms in women with breast cancer. This trial is to determine whether hypnotherapy, administered in a standard way, can improve the frequency of hot flashes and breast cancer specific quality of life in women diagnosed with pre-menopausal breast cancer. We propose to evaluate this through a pilot feasibility study which will randomize participants to an eight week course of gabapentin or hypnosis.
Dates
| Last Verified: | 04/30/2013 |
| First Submitted: | 07/02/2008 |
| Estimated Enrollment Submitted: | 07/02/2008 |
| First Posted: | 07/08/2008 |
| Last Update Submitted: | 05/13/2013 |
| Last Update Posted: | 06/23/2013 |
| Date of first submitted results: | 03/04/2012 |
| Date of first submitted QC results: | 05/13/2013 |
| Date of first posted results: | 06/23/2013 |
| Actual Study Start Date: | 06/30/2008 |
| Estimated Primary Completion Date: | 05/31/2011 |
| Estimated Study Completion Date: | 05/31/2011 |
Condition or disease
Intervention/treatment
Behavioral: Hypnotherapy
Drug: Gabapentin
Phase
Arm Groups
| Arm | Intervention/treatment |
|---|---|
| Experimental: Hypnotherapy Patients randomized to the experimental arm were scheduled for three one-hour inductions by a single hypnotherapist, each one week apart. Standardized outlines were used for each induction. The second and third sessions also began with a standardized induction, followed by the establishment of an "anchor," or physical reference point (forefinger to thumb), used to invoke images of coolness, which were individualized according to patient preference.
Patients were also instructed by the same hypnotherapist in self-hypnosis and guided imagery techniques to be used at home with the assistance of standardized audio compact disks. Participation lasted eight weeks. | Behavioral: Hypnotherapy Patients randomized to the hypnosis arm of the study will undergo individually three one-hour sessions with a certified hypnotherapist. These sessions will be one week apart. surveys. The therapist will be prohibited from asking subjects about clinical responses to the hypnosis sessions. The patients will also be instructed on self-hypnosis techniques to be used at home. |
| Active Comparator: Gabapentin Patients randomized to the gabapentin arm were prescribed 900mg of the drug daily (300 mg by mouth three times daily). | Drug: Gabapentin Patients randomized to the gabapentin arm will be prescribed 900mg of the drug daily (300 mg by mouth three times daily). This dose has been shown to be more effective than 300mg daily. Larger doses have not been evaluated in this population, and may be associated with a more significant side-effect profile. The prescription for gabapentin will be provided at the patient's enrollment appointment. The patients will take gabapentin as prescribed daily for the study-enrollment period, which is 8 weeks. |
Eligibility Criteria
| Ages Eligible for Study | 18 Years To 18 Years |
| Sexes Eligible for Study | Female |
| Accepts Healthy Volunteers | Yes |
| Criteria | Inclusion criteria: - Women with histologic confirmation of a diagnosis of infiltrating carcinoma of the breast are eligible for participation. - Women with non-invasive or pre-invasive lesions of the breast, including but not limited to ductal carcinoma in situ (DCIS), atypical ductal hyperplasia (ADH) or lobular carcinoma in situ (LCIS) are eligible for participation. - Women with a known breast cancer susceptibility gene (eg, BRCA) mutation or strong family history of breast cancer are eligible. - Any woman age 60 years or more who cannot take estrogen therapy because of a real or perceived risk of developing breast cancer are eligible. - Women under the age of 60 with a Gail model score of 1.6% or more are eligible. - Subjective report of at least one daily hot flash. - Able to provide voluntary informed consent. - ≥ 18 years-old. There will be no upper limit for age inclusion. - Karnofsky performance status > 70%. - Women with a history of breast cancer must have undergone treatment with curative intent. - ≥ 4 weeks from completion of chemotherapy or radiation therapy, where appropriate. - adequate hematopoietic function (ANC ≥ 1500/mm3; Platelets ≥ 100,000/mm3; Hemoglobin ≥ 8 g/dL) - adequate renal and hepatic function [Bilirubin ≤ 1.5 times upper limit of normal (ULN), serum glutamic-oxaloacetic transaminase (SGOT) ≤ 2.5x ULN, Alkaline phosphatase ≤ 2.5x ULN, and Creatinine ≤ 2x ULN]. - No clinical evidence of disease (complete remission). - Patients receiving neoadjuvant therapy will be eligible following completion of all adjuvant chemotherapy if indicated. - Patients receiving hormonal therapy in lieu of or following chemotherapy will be eligible to participate. - Patients must have access to a compact disk player. Exclusion criteria: - History or active secondary cancer within the last 5 years (except for superficial basal cell skin cancers). - Any residual chemotherapy-induced CTCv3.0 Grade 2 or greater non-hematological toxicity. - Unable to give informed consent or unable to adhere to protocol. - Any serious medical or psychiatric illness likely to interfere with participation in this clinical study, concurrent uncontrolled illness, or ongoing or active infection will be excluded. - Any history of alcohol or drug abuse. - Allergy to gabapentin. - History of seizure disorder. |
Outcome
Primary Outcome Measures
1. Number of Daily Hot Flashes [Baseline]
2. Number of Daily Hot Flashes [Week 4]
3. Number of Daily Hot Flashes [Week 8]
4. Hot Flash Severity Score [Baseline]
5. Hot Flash Severity Score [Week 4]
6. Hot Flash Severity Score [Week 8]
Secondary Outcome Measures
1. Hot Flash Related Daily Interference Score (HFRDIS) [Baseline]
2. Hot Flash Related Daily Interference Score (HFRDIS) [Week 4]
3. Hot Flash Related Daily Interference Score (HFRDIS) [Week 8]
