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CompletedNCT03346200KARISMA2Updated Mar 7, 2025Results posted

Low Dose Tamoxifen for Mammographic Density Reduction

A Phase 2 interventional study of Tamoxifen Oral Tablet and Placebo Oral Tablet in Risk Reduction and Mammographic Density Reduction, sponsored by Per Hall. Completed. Open to female participants aged 40 Years to 74 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2025-03-07.

Sponsored by Per Hall · Phase 2, Interventional, and Prevention

From the registry’s dates

  • Registered 1 year after the study started (first participant enrolled Nov 2016, registered Nov 2017).
Phase
Phase 2
Study type
Interventional
Enrollment
1,440
Allocation
Randomized
Ages
40 Years to 74 Years
Sex
Female
01

Study summary

KARISMA2 is a randomized, double-blinded, six-armed placebo controlled study to identify a low dose of tamoxifen, with less side-effects and a density reduction non-inferior to the standard dose of 20 mg.

Read the detailed description

This is a dose determination study aiming to identify the optimal tamoxifen dose for reducing the risk of breast cancer. The change in mammographic density is a very good marker of therapy response. Investigators will test if 1 mg, 2.5 mg, 5 mg and 10 mg reduce the mammographic density to the same extent as 20 mg.

1440 healthy women 40-74 yrs were included when adhering the national Swedish mammography screening program between 2016- 2019. Women were randomized and treated daily for 6 months. Mammograms were taken at baseline and at end of treatment and side effects were measured throughout the study trough schedueled questionnaires and spontaneous AE-reporting.

02

Conditions studied

  • Risk Reduction
  • Mammographic Density Reduction

Keywords

  • Breast cancer
  • Prevention
  • Tamoxifen
03

In context

Risk Reduction Behavior

291 studies on the registry are indexed under Risk Reduction Behavior; 39 are open to participants now.

This study's enrollment of 1,440 is above the median of 201 across 250 interventional studies indexed under Risk Reduction Behavior.

Browse Risk Reduction Behavior studies →

Lead sponsor

This is the only study on the registry with Per Hall as lead sponsor.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
40 Years to 74 Years
Sexes eligible
Female
Accepts healthy volunteers
Yes

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  • Attending the national mammography screening program, i.e. aged 40-74 and has performed a screening mammogram maximum 3 months prior to study inclusion
  • Having a measurable mammographic density, i.e. ≥4.5 % density (volumetric) measured by Volpara
  • must be signed before any study specific assessments have been performed

Exclusion criteria

Exclusion Criteria:

  • Pregnancy at start, during time of study medication and up to 3 months after quitting study medication
  • Breast feeding at start, during time of study medication and up to 3 months after quitting study medication
  • Any previous or current diagnosis of breast cancer (including carcinoma in situ)
  • Mammographic BI-RADS code 3 or above at baseline mammography, or at a diagnostic mammography during time of treatment (the first 6 months of the study)
  • Any previous diagnosis of cancer with the exception of non-melanoma skin cancer and in situ cancer of the cervix
  • Currently using oral oestrogen and progesterone based hormone replacement therapy
  • Current use of hormone with hormones, e.g. hormonal contraceptive pills, or progesterone implants. Hormonal intrauterine devices are accepted.
  • A history of thrombo-embolic disease such as embolies, deep vein thrombosis, stroke, or cardiac arrest.
  • Known APC (Activated protein C )- resistance, an inherited hemostatic disorder
  • A history of major surgery of the breast, e.g. reduction or enlargement, which might affect density measurements
  • Women who have an increased risk of venous thrombosis due to immobilization, e.g. using wheelchair
  • Known uncontrolled diabetes
  • Hypertension at baseline, defined as systolic pressure higher than 140 mm Hg and diastolic higher than 90 mm Hg
  • Use of drugs that interfere with CYP2D6 expression such as Seroxat (paroxetine), Fontex (fluoxetin) and Zyban / Voxra (bupropion)
  • Use of Waran (warfarin)
  • Non-medical approved drugs against hot-flashes including phytooestrogen
  • Not able to understand study information and/or
Terms in these criteria, in plain language(3)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Informed consent

Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.

You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

Contraception

Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.

Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.

TIA (transient ischaemic attack)

A “mini-stroke”: temporary stroke-like symptoms caused by reduced blood flow to part of the brain, spinal cord or eye, without signs of a new stroke on a scan.

Stroke symptoms need emergency care at once, even if they go away.

05

Study design

Phase
Phase 2
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Care provider, Investigator)
Enrollment
1,440 participants (actual)

Study arms

  • Active comparator
    20 mg tamoxifen

    Drug: Tamoxifen Oral Tablet

  • Experimental
    10 mg tamoxifen

    Drug: Tamoxifen Oral Tablet

  • Experimental
    5 mg tamoxifen

    Drug: Tamoxifen Oral Tablet

  • Experimental
    2.5 mg tamoxifen

    Drug: Tamoxifen Oral Tablet

  • Experimental
    1 mg tamoxifen

    Drug: Tamoxifen Oral Tablet

  • Placebo comparator
    0 mg tamoxifen

    Drug: Placebo Oral Tablet

Interventions

  • DrugTamoxifen Oral Tablet

    Randomised dose of tamoxifen 1 pill/day for 180 days

  • DrugPlacebo Oral Tablet

    Randomised dose of tamoxifen 1 pill/day for 180 days

06

What researchers measure

Primary outcomes

  1. Mammograpic Density Change

    Change in mammography density. In particular, we will test for noninferiority in the proportion of women in the intervention arms (placebo, 1 mg, 2.5 mg, 5 mg, 10 mg) who have a density reduction as great as or greater (after 6 months) than the median density reduction in the 20 mg arm.

    Time frame: 6 months treatment

Secondary outcomes

  1. Level of Side Effects

    Assess the level of side effects in the intervention arms compared to the 20 mg arm. Symptoms are reported on a 5-graded Likert score scale in a 48-item symptom questionnaire at Baseline and at End of treatment ( End of treatment= full-filled the 6 month treatment or at time of discontinuation prior to 6 months). The outcome measure is based on the sum in Likert score of five symptoms ('hot flashes', 'cold sweats', 'night sweats', 'vaginal discharge' and 'muscle cramps') which were found to have a significant change from start to the end of treatment in both pre- and postmenopausal women when contrasting the effect of 20 mg tamoxifen compared to women on placebo. The maximum/minimum range of change per symtom is 4 steps increase or decrease. Accordingly, in the Top-5 symtoms the maximum/minimum range is +/- 20. Higher scores mean a worse outcome.

    Time frame: From baseline (7-1days before first tablet) up to 6 months or day of discontionuation (prior to 6 months)

  2. Drop Out Level

    Assess the level of drop out in the intervention arms compared to the 20 mg arm

    Time frame: From initiation of treatment (first tablet) up to 6 months of planned treatment (last tablet)

07

Results

Posted Mar 7, 2025

Participant flow

Participant flow — Overall Study
Milestone20 mg Tamoxifen10 mg Tamoxifen5 mg Tamoxifen2.5 mg Tamoxifen1 mg Tamoxifen0 mg Tamoxifen
Started241243240235239242
Completed171167157159174183
Not completed707683766559

Outcome measures

PrimaryMammograpic Density Change

Change in mammography density. In particular, we will test for noninferiority in the proportion of women in the intervention arms (placebo, 1 mg, 2.5 mg, 5 mg, 10 mg) who have a density reduction as great as or greater (after 6 months) than the median density reduction in the 20 mg arm.

Time frame:
6 months treatment
Reported as:
Mean · Percentage of change
Mammograpic Density Change
Percentage of change20 mg Tamoxifen10 mg Tamoxifen5 mg Tamoxifen2.5 mg Tamoxifen1 mg Tamoxifen0 mg Tamoxifen
Mammograpic Density Change-9.6 (-14.8 to -4.5)-6.8 (-11.8 to -1.7)-1.0 (-6.2 to 4.1)-6.9 (-12.1 to -1.8)-1.0 (-6.1 to 4.1)0.1 (-4.9 to 5.1)
Statistical analysis
  • 20 mg Tamoxifen · one-sided Wald tests · p = <0.01 · Median difference (final values): 52.5 · 97.5% CI 41.9 to 100P-values were corrected for multiple comparisons using the Holm-Bonferroni method. Non-inferiority p-values were declared if less than a=0.025
SecondaryLevel of Side Effects

Assess the level of side effects in the intervention arms compared to the 20 mg arm. Symptoms are reported on a 5-graded Likert score scale in a 48-item symptom questionnaire at Baseline and at End of treatment ( End of treatment= full-filled the 6 month treatment or at time of discontinuation prior to 6 months). The outcome measure is based on the sum in Likert score of five symptoms ('hot flashes', 'cold sweats', 'night sweats', 'vaginal discharge' and 'muscle cramps') which were found to have a significant change from start to the end of treatment in both pre- and postmenopausal women when contrasting the effect of 20 mg tamoxifen compared to women on placebo. The maximum/minimum range of change per symtom is 4 steps increase or decrease. Accordingly, in the Top-5 symtoms the maximum/minimum range is +/- 20. Higher scores mean a worse outcome.

Time frame:
From baseline (7-1days before first tablet) up to 6 months or day of discontionuation (prior to 6 months)
Reported as:
Mean · Likert score change in Top5 Symptoms
Level of Side Effects
Likert score change in Top5 Symptoms20 mg Tamoxifen10 mg Tamoxifen5 mg Tamoxifen2.5 mg Tamoxifen1 mg Tamoxifen0 mg Tamoxifen
Level of Side Effects2.71 (2.29 to 3.13)2.97 (2.50 to 3.45)2.52 (2.07 to 2.97)2.39 (1.94 to 2.85)1.65 (1.24 to 2.06)0.36 (0.32 to 0.68)
SecondaryDrop Out Level

Assess the level of drop out in the intervention arms compared to the 20 mg arm

Time frame:
From initiation of treatment (first tablet) up to 6 months of planned treatment (last tablet)
Reported as:
Count of participants · Participants
Drop Out Level
Participants20 mg Tamoxifen10 mg Tamoxifen5 mg Tamoxifen2.5 mg Tamoxifen1 mg Tamoxifen0 mg Tamoxifen
Drop Out Level656979715853

Adverse events

Collected over From baseline (start of treatment) to end of study (6 months or early termination). Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
20 mg Tamoxifen0/241 (0%)2/241 (0.8%)74/241 (30.7%)
10 mg Tamoxifen0/243 (0%)1/243 (0.4%)70/243 (28.8%)
5 mg Tamoxifen0/240 (0%)2/240 (0.8%)63/240 (26.3%)
2.5 mg Tamoxifen0/235 (0%)1/235 (0.4%)65/235 (27.7%)
1 mg Tamoxifen0/239 (0%)1/239 (0.4%)39/239 (16.3%)
0 mg Tamoxifen0/242 (0%)4/242 (1.7%)40/242 (16.5%)
Most frequent serious events
Most frequent serious events
Event20 mg Tamoxifen10 mg Tamoxifen5 mg Tamoxifen2.5 mg Tamoxifen1 mg Tamoxifen0 mg Tamoxifen
Breast cancerNeoplasms benign, malignant and unspecified (incl cysts and polyps)0/2410/2430/2400/2351/2392/242
PyelonephritisRenal and urinary disorders0/2410/2431/2401/2350/2390/242
Gastric haemorrhageGastrointestinal disorders0/2410/2431/2400/2350/2390/242
Suspected TIAVascular disorders1/2410/2430/2400/2350/2390/242
Superficial thrombosisVascular disorders1/2410/2430/2400/2350/2390/242
Squamous cell carcinomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)0/2410/2430/2400/2350/2391/242
Suspected MyelomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)0/2410/2430/2400/2350/2391/242
Brain tumourNeoplasms benign, malignant and unspecified (incl cysts and polyps)0/2411/2430/2400/2350/2390/242
Most frequent other events
Most frequent other events
Event20 mg Tamoxifen10 mg Tamoxifen5 mg Tamoxifen2.5 mg Tamoxifen1 mg Tamoxifen0 mg Tamoxifen
AE Free textEndocrine disorders36/24121/24317/24027/23515/23920/242
Hot flushEndocrine disorders24/24132/24326/24025/23520/23913/242
Night sweatsEndocrine disorders19/24121/24324/24022/23510/23913/242
Vaginal dischargeEndocrine disorders18/24124/24321/24016/2358/2396/242

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)20 mg Tamoxifen10 mg Tamoxifen5 mg Tamoxifen2.5 mg Tamoxifen1 mg Tamoxifen0 mg TamoxifenTotal
<=18 years0000000
Between 18 and 65 years1811791851811931771096
>=65 years606455544665344
Age, Continuous
Age, Continuous(years)20 mg Tamoxifen10 mg Tamoxifen5 mg Tamoxifen2.5 mg Tamoxifen1 mg Tamoxifen0 mg TamoxifenTotal
Mean55.6 ± 9.555.8 ± 10.055.1 ± 9.754.9 ± 9.754.3 ± 9.460.0 ± 9.955.3 ± 9.7
Sex: Female, Male
Sex: Female, Male(Participants)20 mg Tamoxifen10 mg Tamoxifen5 mg Tamoxifen2.5 mg Tamoxifen1 mg Tamoxifen0 mg TamoxifenTotal
Female2412432402352392421440
Male0000000
Race and Ethnicity Not Collected
Race and Ethnicity Not Collected(Participants)20 mg Tamoxifen10 mg Tamoxifen5 mg Tamoxifen2.5 mg Tamoxifen1 mg Tamoxifen0 mg TamoxifenTotal
Count of participants——————0
08

Study locations

No study locations are listed for this record.

09

References and documents

Publications

  • Eriksson M, Eklund M, Borgquist S, Hellgren R, Margolin S, Thoren L, Rosendahl A, Lang K, Tapia J, Backlund M, Discacciati A, Crippa A, Gabrielson M, Hammarstrom M, Wengstrom Y, Czene K, Hall P. Low-Dose Tamoxifen for Mammographic Density Reduction: A Randomized Controlled Trial. J Clin Oncol. 2021 Jun 10;39(17):1899-1908. doi: 10.1200/JCO.20.02598. Epub 2021 Mar 18. PubMed 33734864 ↗

Study documents

PDFs hosted by the registry, ClinicalTrials.gov.

Individual participant data

Plan to share: No

10

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reached

Ran from Nov 2016 to primary completion in Oct 2019, 35 months.

Results were first posted in Mar 2025, 5 years 5 months after primary completion.

How these figures are worked out, and which studies are left out of them.

Registered
Nov 1, 2017
First posted
Nov 17, 2017
StartActual
Nov 2016
Primary completionActual
Oct 2019
CompletionActual
Dec 2019
Results first posted
Mar 7, 2025
Last update
Mar 7, 2025
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Mar 7, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT03346200
Lead sponsor
Per Hall
Responsible party
Per Hall (Professor, MD, PhD, Karolinska Institutet) — Sponsor-investigator
First posted
Nov 17, 2017
Start date
Nov 2016
Primary completion
Oct 2019
Completion
Dec 2019
Results posted
Mar 7, 2025
Last update
Mar 7, 2025

Study contacts

Per Hall, Professor
principal investigator · Karolinska Institutet

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Mar 2025. You cannot join it, but the record below documents what was studied.

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