Venlafaxine for the Prevention of Depression in Patients With Head and Neck Cancer

NCT05724849 | Withdrawn Phase 2 FDA Drug

• 1 other identifier: 230054
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a pilot double-blinded, randomized, placebo-controlled trial to determine if venlafaxine prevents depression in patients undergoing surgery for Head and Neck Cancer (HNC).

Conditions

Head and Neck Cancer; Depression

Outcome Measures

Primary Outcomes (1)

• Prevention of Depression

  Rate of depression at any time interval within the 4-month post-surgery period in patients with no or mild MDD. This will be assessed using the Patient-Health Questionnaire (PHQ-9) which is scored ranging from 0-27 with a higher score indicating more severe depression. Four months was chosen as the duration to capture the adjuvant radiation period, which is typically 3 months post-surgery.

  4 months post-operatively

Secondary Outcomes (5)

• Treatment of Depression

  4 months post-operatively

• Prevention of Anxiety

  4 months post-operatively

• Prevention of Pain

  4 months post-operatively

• Prevention of Pain

  4 months post-operatively

• Quality of Life Improvement

  4 months post-operatively

Study Arms (3)

Venlafaxine

EXPERIMENTAL

Patients who screen negative or meet criteria for mild MDD are eligible for the randomized control trial (RCT) portion of this study in which patients are randomized into either the intervention (venlafaxine) arm or placebo. Participants randomized into the intervention group will be prescribed a starting dose of venlafaxine immediate release (IR) 75mg once daily. The dosing will be increased at the following rate: Week 1: 75mg in AM Week 2: 75mg BID Week 3: 150mg in AM, 75mg in PM Week 4: 150mg BID For patients with hepatic impairment, severe renal impairment, or end stage kidney disease, the starting dose is 37.5 mg once daily, increased by increments of 37.5 mg per day to reach a maximum of 187.5 mg per day, given in two divided doses.

Drug: Venlafaxine

Placebo

PLACEBO COMPARATOR

Patients who screen negative or meet criteria for mild MDD are eligible for the randomized control trial (RCT) portion of this study in which patients are randomized into either the intervention (venlafaxine) arm or placebo. Participants randomized to the placebo group will receive a placebo capsule with the same dosing schedule as the intervention group.

Drug: Placebo

Observation

OTHER

Patients who screen positive for moderate, moderately-severe, or severe MDD are excluded from the RCT and will be enrolled in the study as an observation cohort. These patients will be offered initiation of venlafaxine and will be referred to our collaborating oncologic psychiatrist. Patients in cohort B will still complete the same patient-reported outcome measures (PROMs) as patients in cohort A, allowing us to collect data and better understand what effects venlafaxine has on patients who are already diagnosed with depression at the start of treatment for HNC.

Drug: Venlafaxine

Interventions

Venlafaxine DRUG

See arm/group description.

Also known as: Effexor

Observation; Venlafaxine

Placebo DRUG

See arm/group description.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• COHORT A (RCT)
• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Male or female, aged 18 years or older
• Have a recently diagnosed cutaneous or mucosal malignancy
• Scheduled to undergo surgical treatment for their malignancy with curative intent
• Ability to take medication orally or via gastric tube feeds
• Willing to adhere to the study drug's dosing protocol
• Score \<10 on the PHQ-9
• COHORT B (Observation cohort)
• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Male or female, aged 18 years or older
• Have a recently diagnosed cutaneous or mucosal malignancy
• Scheduled to undergo surgical treatment for their malignancy with curative intent

You may not qualify if:

• COHORT A (RCT)
• Score \>10 on PHQ-9
• Score between 5-9 on PHQ-9 and elect for psychotherapy
• Age less than 18 years
• Primary malignancy of thyroid or parathyroid origin
• Currently meet diagnostic criteria for psychosis, schizophrenia, or bipolar disorder
• Currently receiving medication as treatment for depression or anxiety including: MAO inhibitors, Linezolid, Other SNRIs or SSRIs, Bupropion
• Known allergic reaction to components of study drug
• Treatment with another investigational drug or other intervention within 30 days
• Females of child-bearing age who are pregnant or nursing
• Inability to speak or understand English
• COHORT B (Observation cohort)
• Score \<10 on PHQ-9
• Unwillingness or inability to take venlafaxine
• Age less than 18 years

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead

Related Publications (11)

• Lydiatt WM, Moran J, Burke WJ. A review of depression in the head and neck cancer patient. Clin Adv Hematol Oncol. 2009 Jun;7(6):397-403.

  PMID: 19606075 BACKGROUND

• Chhabria KS, Carnaby GD. Psychometric validation of the Center for Epidemiological Studies Depression Scale in Head and Neck Cancer patients. Oral Oncol. 2017 Dec;75:158-162. doi: 10.1016/j.oraloncology.2017.11.010. Epub 2017 Nov 15.

  PMID: 29224813 BACKGROUND

• Rieke K, Schmid KK, Lydiatt W, Houfek J, Boilesen E, Watanabe-Galloway S. Depression and survival in head and neck cancer patients. Oral Oncol. 2017 Feb;65:76-82. doi: 10.1016/j.oraloncology.2016.12.014. Epub 2017 Jan 1.

  PMID: 28109472 BACKGROUND

• Archer J, Hutchison I, Korszun A. Mood and malignancy: head and neck cancer and depression. J Oral Pathol Med. 2008 May;37(5):255-70. doi: 10.1111/j.1600-0714.2008.00635.x. Epub 2008 Feb 26.

  PMID: 18312300 BACKGROUND

• Cramer JD, Johnson JT, Nilsen ML. Pain in Head and Neck Cancer Survivors: Prevalence, Predictors, and Quality-of-Life Impact. Otolaryngol Head Neck Surg. 2018 Nov;159(5):853-858. doi: 10.1177/0194599818783964. Epub 2018 Jun 26.

  PMID: 29943677 BACKGROUND

• Friedland CJ. Head and Neck Cancer: Identifying Depression as a Comorbidity Among Patients. Clin J Oncol Nurs. 2019 Feb 1;23(1):99-102. doi: 10.1188/19.CJON.99-102.

  PMID: 30681992 BACKGROUND

• Barber B, Dergousoff J, Slater L, Harris J, O'Connell D, El-Hakim H, Biron VL, Mitchell N, Seikaly H. Depression and Survival in Patients With Head and Neck Cancer: A Systematic Review. JAMA Otolaryngol Head Neck Surg. 2016 Mar;142(3):284-8. doi: 10.1001/jamaoto.2015.3171.

  PMID: 26796781 BACKGROUND

• Lydiatt WM, Denman D, McNeilly DP, Puumula SE, Burke WJ. A randomized, placebo-controlled trial of citalopram for the prevention of major depression during treatment for head and neck cancer. Arch Otolaryngol Head Neck Surg. 2008 May;134(5):528-35. doi: 10.1001/archotol.134.5.528.

  PMID: 18490576 BACKGROUND

• Lydiatt WM, Bessette D, Schmid KK, Sayles H, Burke WJ. Prevention of depression with escitalopram in patients undergoing treatment for head and neck cancer: randomized, double-blind, placebo-controlled clinical trial. JAMA Otolaryngol Head Neck Surg. 2013 Jul;139(7):678-86. doi: 10.1001/jamaoto.2013.3371.

  PMID: 23788218 BACKGROUND

• Panwar A, Rieke K, Burke WJ, Sayles H, Lydiatt WM; Prevention of Depression in Patients Being Treated for Head and Neck Cancer Trial (PROTECT) study group. Identification of Baseline Characteristics Associated With Development of Depression Among Patients With Head and Neck Cancer: A Secondary Analysis of a Randomized Clinical Trial. JAMA Otolaryngol Head Neck Surg. 2018 Nov 1;144(11):1004-1010. doi: 10.1001/jamaoto.2018.2228.

  PMID: 30286230 BACKGROUND

• Smith EM, Pang H, Cirrincione C, Fleishman S, Paskett ED, Ahles T, Bressler LR, Fadul CE, Knox C, Le-Lindqwister N, Gilman PB, Shapiro CL; Alliance for Clinical Trials in Oncology. Effect of duloxetine on pain, function, and quality of life among patients with chemotherapy-induced painful peripheral neuropathy: a randomized clinical trial. JAMA. 2013 Apr 3;309(13):1359-67. doi: 10.1001/jama.2013.2813.

  PMID: 23549581 BACKGROUND

MeSH Terms

Conditions

Head and Neck Neoplasms; Depression

Interventions

Venlafaxine Hydrochloride

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Cyclohexanols; Hexanols; Fatty Alcohols; Alcohols; Organic Chemicals; Phenethylamines; Ethylamines; Amines; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Lipids

Study Officials

• Michael C Topf, MD

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor, Department of Otolaryngology

Study Record Dates

• First Submitted: January 31, 2023
• First Posted: February 13, 2023
• Study Start: August 1, 2023
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026
• Last Updated: January 18, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share