Acupuncture Versus Sham Acupuncture or Usual Care for Antiandrogen-Induced Hot fLashes in Prostate Cancer (AVAIL)

Study Overview
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Brief Summary
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Hot flashes are a common and debilitating symptom among prostate cancer patients undergoing androgen deprivation therapy (ADT). Strong evidence from multiple rigorously designed studies indicated that venlafaxine provides partial relief, but the tolerability is poor when the dose is not tapered. Hence, an alternative therapy is needed. Previous studies reported that acupuncture may be helpful in the management of hot flashes. However, the insufficient randomized controlled trial limited the quality of evidence.

Detailed Description
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The number of men surviving after being diagnosed with prostate cancer has increased rapidly. According to population-based cancer registry data, 10-year survival has tripled in the past 40 years in the UK. Androgen deprivation therapy (ADT) is a mainstay of prostate cancer treatment and has been shown in randomized controlled trials to improve overall survival when used with radiation for intermediate- and high-risk localized disease, as well as locally advanced and node-positive disease, and after surgery for the node-positive disease. Although ADT can improve survival, it can also cause significant morbidity and a decrement in quality of life. One of the most bothersome side effects is hot flashes. They are experienced as sudden and transient episodes of heat and sweating, with possible co-occurring palpitations and anxiety, usually persist long-term. The prevalence estimated that 44-80% of patients undergoing ADT report hot flashes and up to 27% report this as the most troublesome adverse effect. Although hot flashes are not fatal morbidity, it may interfere with adherence to lifesaving therapies or ablative therapies that are used to prevent or treat cancer. Currently, most intervention studies for hot flashes have evaluated treatments in breast cancer patients or women who are postmenopausal. Venlafaxine, a selective serotonin reuptake inhibitor, appears to be effective and safe in both breast cancer women and prostate cancer men with hot flashes. It has been recommended for practice in men with strong evidence from multiple rigorously designed studies. However, some prostate cancer patients cannot take venlafaxine because of side effects such as nausea, headache, dry mouth, dizziness, insomnia, and constipation. Thus, an alternative therapy is needed. A systematic review identified six studies of acupuncture for hot flashes, of which none were randomized and placebo-controlled. Although acupuncture is a nonpharmacologic therapy and has been confirmed that could be helpful in the management of hot flashes among breast cancer survivors, there is no placebo acupuncture-controlled trials demonstrating its efficacy in men.

Official Title
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Acupuncture Versus Sham Acupuncture or Usual Care for Antiandrogen-Induced Hot fLashes in Prostate Cancer (AVAIL): a Multicenter Randomized Controlled Trial

Conditions
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Hot Flashes, Prostate Cancer, Acupuncture

Intervention / Treatment
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* Device: Acupuncture
* Device: Sham Acupuncture


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients aging from 18 to 75 years diagnosed with prostate cancer undergoing ADT; with an average of 3 or more hot flashes a day for at least 3 days before enrollment and no other clinically significant disease; not receiving any medications for hot flashes nor did they have a previous history of acupuncture treatment. Exclusion Criteria: hormonal treatment other than GnRH analogue daily treatment with psychotropic drugs newly started or changed alternative medications with possible effects on flushes uncontrolled hypertension or metabolic disease inability to move/lie on the side, and treatment with anticoagulants or pacemaker.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients will be randomly 2:1:1 allocated to the verum acupuncture (n=60), sham acupuncture (n=30), or usual care (n=30) group.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Acupuncture<br>Licensed acupuncturists with more than 5 years of experience will be responsible for administering interventions three times per week for 6 weeks. The needles (30 or 40 mm and 0.25 mm gauge; Soochow, Hwato) will be inserted and manipulated until De Qi, a sensation of soreness and tingling. Acupuncture was defined as targeting the 10 bilateral acupuncture points: Xinshu (BL15), Shenshu (BL23), Zhongliao (BL33), Sanyinjiao (SP6), Yinlingquan (SP9). The needle will be left in place for 30 minutes with brief manipulation at the beginning, middle, and end of therapy. | Device: Acupuncture<br>* For the active acupuncture group, the acupuncturist chose standard points depending on subjects' preferred positions. In addition, up to four acupuncture points were chosen on the basis of subjects' other presenting symptoms (such as fatigue, insomnia, or erectile dysfunction). The needles (30 or 40 mm and 0.25 mm gauge; Soochow, Hwato) will be inserted and manipulated until De Qi, a sensation of soreness and tingling.<br>|
| Sham Comparator: Sham Acupuncture<br>Treatment will be the same for the sham acupuncture, except for the following: the acupuncturist selected the same number of nonacupuncture, nontrigger points. Instead of eliciting De Qi, the needles will be minimally manipulated to avoid eliciting sensations other than initial contact with skin. | Device: Sham Acupuncture<br>* Treatment will be the same for the sham acupuncture, except for the following: the acupuncturist selected the same number of nonacupuncture, nontrigger points. Instead of eliciting De Qi, the needles will be minimally manipulated to avoid eliciting sensations other than initial contact with skin.<br>* Other names: Non-penetrating Acupuncture;|
| No Intervention: Usual Care<br>Patients receiving usual care received neither acupuncture nor sham acupuncture. After the 6-week assessment, patients will be offered the option to receive acupuncture treatment as the acupuncture group. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Weekly mean hot flash symptom severity score (HFSSS) | The HFSSS is defined as the product of hot frequency and hot severity. The severity of hot flashes is assessed based on the duration of hot flashes and physical and emotional symptoms; it is scored as mild, moderate, severe, and very severe (range 1-4, from mild to very severe). | Baseline to week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Weekly mean hot flash symptom severity score (HFSSS) | The HFSSS is defined as the product of hot frequency and hot severity. The severity of hot flashes is assessed based on the duration of hot flashes and physical and emotional symptoms; it is scored as mild, moderate, severe, and very severe (range 1-4, from mild to very severe). | Baseline to week 14 | 
| Response rate of HFSSS | The responders will be defined according to a 50% reduction of HFSSS | Baseline, week 6, and week 14 | 
| Functional Assessment of Cancer Therapy-Prostate (FACT-P) | The Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire is a relevant, worldwide tool used for assessing the health-related quality of life in men with prostate cancer. | Baseline, week 6, and week 14 | 
| International Index of Erectile Function (IIEF-5) | The IIEF-15 comprises 15 items divided into 5 domains: erectile function, orgasmic function, sexual desire, intercourse satisfaction, and overall satisfaction, respectively. The IIEF-5 comprises 5 items from the IIEF-15, 4 from the erectile function domain, and 1 from intercourse satisfaction. Response options for each item ranged from 1 to 5, and occasionally the option 0 depicting no sexual stimulation/intercourse, the scores are summed. | Baseline, week 6, and week 14 | 
| The Zung Self-Rating Anxiety Scale (SAS) | The SAS consists of 20 items that assess common symptoms of anxiety, such as tension, fear, worry, and nervousness. Each item is rated on a Likert-type scale ranging from 1 to 4. Scores on the scale can rage from 20 to 80, with higher scores indicating more severe symptoms of anxiety. | Baseline, week 6, and week 14 | 
| The Zung Self-Rating Depression Scale (SDS) | The SDS is a 20-item measure, with each item rated on a 4-point scale. It requires approximately 5-10 minutes to complete. Ranges for mild to moderate depression, moderate to severe depression, and severe depression are 50-59, 60-69, and over 70, respectively. | Baseline, week 6, and week 14 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prostate Cancer, Hot Flashes, Acupuncture, Randomized Controlled Trial