The Effects of HER2 Receptor Signaling on Human Brown Fat Activity

NCT06222957 | Recruiting

• 1 other identifier: H-23055495
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The objective of this observational study is to investigate the significance of the HER2 receptor for brown fat activity in humans. Our preliminary data clearly demonstrates that the ErbB signaling pathway, which includes the HER2 receptor, strongly promotes development and function of cultured human BAT cells. The HER2 receptor is a part of the ErbB signaling pathway, and antibodies against thee HER2 receptor are a part of the standard treatment for HER2-positive breast cancer. Therefore, the hypothesis is that the activity of brown fat will be reduced in patients treated with HER2 blocking antibody compared to patients who are not treated with HER2 blocking antibody. The present study simply takes advantage of the treatment protocol to explore the contribution of the HER2 receptor in the development of brown adipose tissue in humans. Participants will complete two testing days, one before and one after their treatment period of approx. one year. On the testing days, identification of brown fat activity will be performed using cooling and infrared thermography. In addition, resting metabolic rate and a glucose tolerance test will be performed. Since presence of active brown adipose tissue in humans is inversely related to obesity, total and visceral fat mass, plasma glucose levels, presence of cardiovascular disease and diabetes status, it is of great importance to investigate the molecular mechanisms for development of brown fat tissue and may lead to discovery of novel strategies to counteract obesity and obesity related disorders.

Conditions

Breast Cancer

Keywords

HER2 receptor; HER2 receptor positive; Brown adipose tissue; Human brown fat; Trastuzumab; Cooling; Infrared thermography

Outcome Measures

Primary Outcomes (1)

• BAT activity

  Difference in cold-induced BAT activity between HER2+ breast cancer patients and HER2- breast cancer controls measured with infrared thermography (temperature difference).

  One year

Secondary Outcomes (7)

• Change in weight

  One year

• Change fat mass

  One year

• Resting energy expenditure

  One year

• Cold induced energy expenditure

  One year

• Glycemic control (OGTT) - Insulin

  One year

Study Arms (2)

HER2 positive group

HER2-positive (HER2+) and Estrogen receptor-positive (ER+) breast cancer patients undergoing adjuvant chemotherapy including trastuzumab.

Other: None (Observational study)

Control group

HER2-negative breast cancer patients (HER2-) and Estrogen receptor-positive (ER+) breast cancer patients undergoing adjuvant chemotherapy without trastuzumab.

Other: None (Observational study)

Interventions

None (Observational study) OTHER

Both groups recieve standard care as decided by the responsible clinicians at the department of Oncology. The course of the treatment is completely independent from the observations in the present study.

Control group; HER2 positive group

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients with histologically confirmed breast cancer (HER2+/HER2-/ER+) sheduled for adjuvant treatment at Rigshospitalet, Copenhagen, Denmark

You may qualify if:

• Female
• Age \> 18 years
• Histologically confirmed breast cancer
• No prior neoadjuvant treatment
• Estrogen receptor positive (\>1%)
• Presence of cold activated brown fat as evidenced by a change in Δtemp. of \>1°C (post cooling - precooling temperature).
• HER2 positive group: HER2-positive (HER2+) and Estrogen receptor-positive (ER+) breast cancer patients (N = 15):
• HER2 positive breast cancer as defined by ASCO/CAP criteria
• Scheduled to receive adjuvant chemotherapy, a total of 17 series of trastuzumab and endocrine treatment
• Control group: HER2-negative breast cancer patients (HER2-) and Estrogen receptor-positive (ER+) breast cancer patients (N = 15):
• HER2 negative breast cancer as defined by ASCO/CAP criteria
• Scheduled to receive adjuvant chemotherapy and endocrine treatment

You may not qualify if:

• Any other cancer (excluding carcinoma in situ and radically operated localised squamous skin cancer) with clinical activity within the last 2 years
• Metastatic breast cancer
• Metabolic diseases such as diabetes (exceptions can be made if the disease is well treated, assessed by the clinically responsible medical doctor (see section 18))
• Regular use of prednisolone - use in relation to chemotherapy only is ok
• Pregnancy
• Untreated or dysregulated hypertension defined as outpatient clinic systolic BP \> 155 and diastolic BP \> 95
• Clinically significant ventricular or atrial arrhythmia
• Untreated coronary artery disease or angina pectoris
• Symptomatic heart failure (NYHA ≥ 2)
• Known cold urticaria

Sponsors & Collaborators

• Rigshospitalet, Denmark: lead

Study Sites (1)

Centre for Physical Activity Research (CFAS), Rigshospitalet, University of Copenhagen

Copenhagen, 2100, Denmark

RECRUITING

Biospecimen

Retention: SAMPLES WITHOUT DNA

We will draw blood samples, but not for genetic analysis

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Observation

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Methods; Investigative Techniques

Study Officials

• Søren Nielsen, MSc., Ph.D.

  Centre for Physical Activity Research, Rigshospitalet, University of Copenhagen, Denmark

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tora Ida Henriksen, MSc., Ph.D.

CONTACT

+45 35 45 73 78; tora.ida.henriksen@regionh.dk

Christina Yfanti, MSc, PhD

CONTACT

+45 35 45 76 26; christina.yfanti@regionh.dk

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Primary Investigator

Study Record Dates

• First Submitted: January 16, 2024
• First Posted: January 25, 2024
• Study Start: November 14, 2024
• Primary Completion: March 1, 2026
• Study Completion: March 1, 2026
• Last Updated: November 19, 2024

Record last verified: 2024-11

Locations

DK (1)