Erythropoietic ProtoporphyriaPhase 2NCT05020184
Effect of Oral Cimetidine in the Protoporphyrias
A Phase 2 study testing Cimetidine in people with Erythropoietic Protoporphyria and X-linked Protoporphyria, run by Amy K. Dickey, M.D. at 3 sites in United States.
Trial summary
Erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP) result from genetic defects of heme biosynthesis that cause life-long, painful cutaneous sensitivity to light. Read more about this study
- Who is it for?
- Ages 15 years and older
- Conditions the study is for
- Erythropoietic Protoporphyria, X-linked Protoporphyria
- What is being tested?
- Cimetidine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 26 participants
- Where
- 3 sitesUnited States
- Study dates
- 14 Jun 2022to 24 Apr 2025
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 15 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Prior enrollment or co-enrollment in the Longitudinal Study of the Porphyrias (PC Study 7201) with a confirmed diagnosis of EPP or XLP
- Male or female age ≥15 years at screening
- Characteristic history of non-blistering cutaneous photosensitivity
- Willing and capable of giving informed consent and following procedures described in the protocol
Who cannot join
- Participants not willing to expose themselves to light to the point of prodromal symptoms at least weekly
- History of liver or bone marrow transplant or clinically significant liver dysfunction as determined by the Investigator
- Known or suspected allergy or intolerance to cimetidine
- Use of any other experimental therapy in the past 3 months at screening
- Use of cimetidine within the past 3 months at screening
- Individuals with elevations of porphyrins in plasma or erythrocytes due to other diseases (i.e., secondary porphyrinemia) such as liver and bone marrow diseases
Show all 11Show fewer
- Patients with any clinically significant comorbid conditions, which in the opinion of the Investigator, precludes participation
- Treatment with any drugs or supplements (Appendix 1) that in the opinion of the Investigator can interfere with subject safety or the objectives of the study
- The participant either does not have a smartphone or is not willing to use his/her smartphone for the study
- Women who are pregnant, breastfeeding, or actively planning to become pregnant
- Individuals with moderate to severe renal insufficiency
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
University of Texas Medical Branch
Galveston, Texas, 77555
Atrium Health Wake Forest Baptist Medical Center
Winston-Salem, North Carolina, 27157
About this study
Erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP) result from genetic defects of heme biosynthesis that cause life-long, painful cutaneous sensitivity to light. The objective of this study is to determine the efficacy and safety of oral cimetidine administration for treatment of the protoporphyrias. Efficacy will be based on protoporphyrin levels, photosensitivity, and quality of life questionnaires.
Funding Source- FDA OOPD
Read the detailed description
Erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP) are genetic defects of heme biosynthesis that cause life-long, painful cutaneous sensitivity to light. EPP and XLP, collectively called the protoporphyrias, result in the accumulation of the light-sensitive molecule protoporphyrin IX initially in the bone marrow during hemoglobin synthesis and secondarily in erythrocytes, plasma, and the liver. In addition to photosensitivity, protoporphyria can also result in anemia, gallstones, and liver failure. No therapy has been demonstrated to reduce protoporphyrin levels or prevent the potentially life-threatening complications of EPP. Cimetidine has gained attention as a possible treatment for human porphyrias because of a potential off-target effect of inhibition of delta-aminolevulinate synthase (ALAS), the first enzyme of heme biosynthesis. This inhibition was first described in vitro; however, case reports of benefit in EPP have been anecdotal and uncontrolled. Therefore, the objective of this study is to determine the efficacy and safety of oral cimetidine administration in the protoporphyrias. Efficacy will be based on protoporphyrin levels, photosensitivity, and quality of life questionnaires. If the results are positive, this would be the first study providing quality evidence for an agent acting as a disease-modifying therapy for EPP. The study is also attractive because it repurposes an already approved drug with few side effects to treat a rare human disease.
The study design is a prospective, blinded, randomized, 2x2 cross-over design comparing cimetidine to placebo in patients with protoporphyria. Eligible protoporphyria patients will be randomized with equal allocation to one of two treatment sequences that will be administered over two 3-month study periods. Randomization will be stratified by site and permuted block randomization will be used to prevent chronological bias. Patients randomized to sequence 1 will receive placebo during period 1 and cimetidine during period 2. Patients randomized to sequence 2 will receive cimetidine during period 1 and placebo during period 2. Between periods, to eliminate any carry-over effects from the treatment administered in period 1, a wash-out period of 3 months will occur in which all patients receive neither cimetidine nor placebo. Three months was selected for each study period and for the wash-out period because of the rapid decline in protoporphyrin in red cells over the lifespan of the red cell (120 days), as well as to account for the time frame needed to measure light sensitivity in EPP.
- Being tested
- Cimetidine, Placebo
- Keywords
- Erythropoietic Protoporphyria, X-linked Protoporphyria, EPP, Cimetidine, Photosensitivity
- Medical subject headings
- Protoporphyria, Erythropoietic, Protoporphyria, Erythropoietic, X-Linked Dominant, Photosensitivity Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CimetidineDrug
Also called Tagament
Oral Cimetidine 800mg twice daily.
PlaceboDrug
Placebo twice daily
| Study group | Role | What they receive |
|---|---|---|
| Cimetidine | Active comparator | Cimetidine 800mg orally twice daily Receives: Drug: Cimetidine |
| Placebo | Placebo comparator | Placebo capsule orally twice daily Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Change in Erythrocyte Total Protoporphyrin Level
Percent change in erythrocyte total protoporphyrin levels after treatment period versus before.
Measured: Before and after each 3-month treatment period
Secondary outcomes (5)
Time to Prodrome
Mean daily self-reported outdoor time, in minutes, before EPP/XLP prodrome onset during the last two months of each treatment period, including days without symptoms.
Measured: Last 2 months of each treatment period
Change in PROMIS-57 v2 Domain T-scores From Pre-treatment to End of Each 3-month Treatment Period
PROMIS-57 v2 assesses 7 health domains: Physical Function, Anxiety, Depression, Fatigue, Sleep Disturbance, Ability to Participate in Social Roles and Activities, and Pain Interference. Domain scores are converted to standardized T-scores with a U.S. general population mean of 50 and standard deviation of 10. Higher scores indicate worse outcomes for Anxiety, Depression, Fatigue, Sleep Disturbance, and Pain Interference, and better outcomes for Physical Function and Ability to Participate in Social Roles and Activities. PROMIS-57 v2 was administered immediately before and at the end of each 3-month treatment period. End-of-period PROMIS-57 v2 domain T-scores were analyzed using mixed-effects linear models adjusted for the immediately pre-treatment PROMIS-57 v2 domain T-score for that treatment period, with treatment as a fixed effect and participant as a random effect. Reported values represent least squared means for change in T-score for the cimetidine and placebo treatment periods.
Measured: Immediately before and at the end of the 3-month cimetidine treatment period, and immediately before and at the end of the 3-month placebo treatment period
Change in PROMIS-57 v2 Pain Intensity Scores From Pre-treatment to End of Each 3-month Treatment Period
PROMIS-57 v2 Pain Intensity is a single item scored from 0 to 10, with higher scores indicating worse pain intensity. The instrument-defined possible score range is 0 to 10. This question was administered immediately before and at the end of each 3-month treatment period in this crossover trial. End-of-period PROMIS-57 v2 Pain Intensity scores were analyzed using mixed-effects linear models adjusted for the immediately pre-treatment Pain Intensity score for that treatment period, with treatment as a fixed effect and participant as a random effect. Reported values represent least squared means for change in Pain Intensity scores for the cimetidine and placebo treatment periods.
Measured: Immediately before and at the end of the 3-month cimetidine treatment period, and immediately before and at the end of the 3-month placebo treatment period
Number of Phototoxic Reactions Per Participant During the Last 2 Months of Each Treatment Period
For each participant, the number of phototoxic reactions during the last 2 months of each 3-month treatment period was recorded. In this crossover trial, the reported outcome compares the number of phototoxic reactions per patient during cimetidine with the number during placebo.
Measured: Last 2 months of the 3-month cimetidine treatment period and last 2 months of the 3-month placebo treatment period
Blue Light Dose
Average daily outdoor blue light dose before EPP/XLP prodrome onset during the last two months of each treatment period, including days without symptoms. Dose data for the day were excluded if the patient did not wear the dosimeter for the entire day.
Measured: Last 2 months of each treatment period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Aug 2021
- Study start14 Jun 2022
- Primary completion24 Apr 2025
- Study completion24 Apr 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Erythropoietic ProtoporphyriaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- The study design is a multicenter, prospective, randomized, double-blind, placebo-controlled, crossover trial of oral cimetidine 800mg twice daily versus placebo
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amy K. Dickey, M.D.
- Sponsor type
- University, hospital or other
- Collaborators
- Wake Forest University Health Sciences, The University of Texas Medical Branch, Galveston
- Responsible party
- Sponsor-investigator, Amy K. Dickey, M.D., Massachusetts General Hospital
- Investigators
- Amy K Dickey, MD, Principal investigator, Massachusetts General HospitalKarl Anderson, MD, Principal investigator, University of Texas
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05020184
- Sponsor's protocol ID
- 2021P002095
- Other IDs
- PC7211, 1R01FD007287-01
- Status last verified
- Aug 2026
- First submitted
- 26 Jul 2021
- Last updated
- 4 Sep 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data that underlie the results reported in the published article, as well as the study protocol and statistical analysis plan, may be shared, after de-identification (text, tables, figures, and appendices), if meeting the time frame and access criteria listed below.
Study at a glance
From the registry record, last updated by the sponsor on 4 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Oral Cimetidine in the Protoporphyrias
- ClinicalTrials.gov ID
- NCT05020184
- Acronym / sponsor ID
- 2021P002095
- Keywords
- Erythropoietic Protoporphyria, X-linked Protoporphyria, EPP, Cimetidine, Photosensitivity
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- Amy K. Dickey, M.D.University, hospital or other
- Collaborators
- Wake Forest University Health Sciences, The University of Texas Medical Branch, Galveston
- Study start
- 14 Jun 2022 (actual)
- Primary completion
- 24 Apr 2025 (actual)
- Study completion
- 24 Apr 2025 (actual)
- First posted
- 25 Aug 2021 (actual)
- Results
- Posted 29 Jun 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP) result from genetic defects of heme biosynthesis that cause life-long, painful cutaneous sensitivity to light. The objective of this study is to determine the efficacy and safety of oral cimetidine administration for treatment of the protoporphyrias. Efficacy will be based on protoporphyrin levels, photosensitivity, and quality of life questionnaires.
Funding Source- FDA OOPD
Detailed description
Erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP) are genetic defects of heme biosynthesis that cause life-long, painful cutaneous sensitivity to light. EPP and XLP, collectively called the protoporphyrias, result in the accumulation of the light-sensitive molecule protoporphyrin IX initially in the bone marrow during hemoglobin synthesis and secondarily in erythrocytes, plasma, and the liver. In addition to photosensitivity, protoporphyria can also result in anemia, gallstones, and liver failure. No therapy has been demonstrated to reduce protoporphyrin levels or prevent the potentially life-threatening complications of EPP. Cimetidine has gained attention as a possible treatment for human porphyrias because of a potential off-target effect of inhibition of delta-aminolevulinate synthase (ALAS), the first enzyme of heme biosynthesis. This inhibition was first described in vitro; however, case reports of benefit in EPP have been anecdotal and uncontrolled. Therefore, the objective of this study is to determine the efficacy and safety of oral cimetidine administration in the protoporphyrias. Efficacy will be based on protoporphyrin levels, photosensitivity, and quality of life questionnaires. If the results are positive, this would be the first study providing quality evidence for an agent acting as a disease-modifying therapy for EPP. The study is also attractive because it repurposes an already approved drug with few side effects to treat a rare human disease.
The study design is a prospective, blinded, randomized, 2x2 cross-over design comparing cimetidine to placebo in patients with protoporphyria. Eligible protoporphyria patients will be randomized with equal allocation to one of two treatment sequences that will be administered over two 3-month study periods. Randomization will be stratified by site and permuted block randomization will be used to prevent chronological bias. Patients randomized to sequence 1 will receive placebo during period 1 and cimetidine during period 2. Patients randomized to sequence 2 will receive cimetidine during period 1 and placebo during period 2. Between periods, to eliminate any carry-over effects from the treatment administered in period 1, a wash-out period of 3 months will occur in which all patients receive neither cimetidine nor placebo. Three months was selected for each study period and for the wash-out period because of the rapid decline in protoporphyrin in red cells over the lifespan of the red cell (120 days), as well as to account for the time frame needed to measure light sensitivity in EPP.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- The study design is a multicenter, prospective, randomized, double-blind, placebo-controlled, crossover trial of oral cimetidine 800mg twice daily versus placebo
| Arm | Type | Receives |
|---|---|---|
| Cimetidine | Active comparator | Drug: CimetidineCimetidine 800mg orally twice daily |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo capsule orally twice daily |
Who may qualify
- Ages
- 15 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- Prior enrollment or co-enrollment in the Longitudinal Study of the Porphyrias (PC Study 7201) with a confirmed diagnosis of EPP or XLP
- Male or female age ≥15 years at screening
- Characteristic history of non-blistering cutaneous photosensitivity
- Willing and capable of giving informed consent and following procedures described in the protocol
Key exclusion criteria (11 listed)
- Participants not willing to expose themselves to light to the point of prodromal symptoms at least weekly
- History of liver or bone marrow transplant or clinically significant liver dysfunction as determined by the Investigator
- Known or suspected allergy or intolerance to cimetidine
- Use of any other experimental therapy in the past 3 months at screening
- Use of cimetidine within the past 3 months at screening
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CimetidineAlso: TagamentOral Cimetidine 800mg twice daily. | Drug | Cimetidine |
| PlaceboPlacebo twice daily | Drug | Placebo |
Primary outcome
Percent Change in Erythrocyte Total Protoporphyrin Level
Time frame: Before and after each 3-month treatment period
Percent change in erythrocyte total protoporphyrin levels after treatment period versus before.
5 secondary outcomes
Time to Prodrome
Time frame: Last 2 months of each treatment period
Change in PROMIS-57 v2 Domain T-scores From Pre-treatment to End of Each 3-month Treatment Period
Time frame: Immediately before and at the end of the 3-month cimetidine treatment period, and immediately before and at the end of the 3-month placebo treatment period
Change in PROMIS-57 v2 Pain Intensity Scores From Pre-treatment to End of Each 3-month Treatment Period
Time frame: Immediately before and at the end of the 3-month cimetidine treatment period, and immediately before and at the end of the 3-month placebo treatment period
Number of Phototoxic Reactions Per Participant During the Last 2 Months of Each Treatment Period
Time frame: Last 2 months of the 3-month cimetidine treatment period and last 2 months of the 3-month placebo treatment period
Blue Light Dose
Time frame: Last 2 months of each treatment period
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Sep 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. Individual participant data that underlie the results reported in the published article, as well as the study protocol and statistical analysis plan, may be shared, after de-identification (text, tables, figures, and appendices), if meeting the time frame and access criteria listed below.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Amy K Dickey, MD principal investigator
Massachusetts General Hospital
Karl Anderson, MD principal investigator
University of Texas
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Cimetidine in people with Erythropoietic Protoporphyria and X-linked Protoporphyria, run by Amy K. Dickey, M.D. at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Jun 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent Change in Erythrocyte Total Protoporphyrin Level (time frame: Before and after each 3-month treatment period). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Sep 2026.